Hemodialysis system with cassette-based blood and dialyste pumping

ABSTRACT

A hemodialysis system includes: (i) a dialyzer; (ii) a dialysate source; a dialysate pump; (iii) a dialysate cassette operatively connected to the dialysate pump such that the dialysate pump can pump dialysate through the dialysate cassette when the dialysate cassette is in fluid communication with the dialysate source, the dialysate cassette in fluid communication with the dialyzer; (iv) a blood pump; and (v) a blood cassette separate from the dialysate cassette, the blood cassette operatively connected to the blood pump such that the blood pump can pump blood through the blood cassette, the blood cassette including a housing, the housing including a from-patient tube connector, a to-patient tube connector, a saline/priming tube connector, a to-dialyzer tube connector, a from-dialyzer tube connector, and an internal air separation chamber.

PRIORITY CLAIM

This application claims priority to and the benefit as a continuation ofU.S. patent application Ser. No. 11/530,842, entitled “Medical FluidSystem With Flexible Sheeting Disposable Unit”, filed Sep. 11, 2006,which is a continuation-in-part of U.S. patent application Ser. No.10/982,170. entitled “High Convection Home Hemodialysis/HemofiltrationAnd Sorbent System”, filed Nov. 4, 2004, which claims priority to andthe benefit of U.S. Provisional Patent Application No. 60/517,730, filedNov. 5, 2003, entitled “High Convection Home Hemodialysis/HemofiltrationAnd Sorbent System”, the entire contents of each of which are herebyincorporated by reference and relied upon.

BACKGROUND

The examples discussed below relate generally to medical fluid delivery.More particularly, the examples disclose systems, methods andapparatuses for the control of fluid flow in kidney failure treatmentsystems.

Due to various causes, a person's renal system can fail. Renal failureproduces several physiological derangements. The balance of water,minerals and the excretion of daily metabolic load is no longer possibleand toxic end products of nitrogen metabolism (urea, creatinine, uricacid, and others) can accumulate in blood and tissue.

Kidney failure and reduced kidney function have been treated withdialysis. Dialysis removes waste, toxins and excess water from the bodythat would otherwise have been removed by normal functioning kidneys.Dialysis treatment for replacement of kidney functions is critical tomany people because the treatment is life saving.

Hemodialysis and peritoneal dialysis are two types of dialysis therapiesused commonly to treat loss of kidney function. A hemodialysis (“HD”)treatment utilizes the patient's blood to remove waste, toxins andexcess water from the patient. The patient is connected to ahemodialysis machine and the patient's blood is pumped through themachine. Catheters are inserted into the patient's veins and arteries sothat blood can flow to and from the hemodialysis machine. The bloodpasses through a dialyzer of the machine, which removes waste, toxinsand excess water from the blood. The cleaned blood is returned to thepatient. A large amount of dialysate, for example about 120 liters, isconsumed to dialyze the blood during a single hemodialysis therapy.Hemodialysis treatment lasts several hours and is generally performed ina treatment center about three or four times per week.

Another form of kidney failure treatment involving blood ishemofiltration (“HF”), which is an alternative kidney failure therapythat relies on a convective transport of toxins from the patient'sblood. This therapy is accomplished by adding substitution orreplacement fluid to the extracorporeal circuit during treatment(typically ten to ninety liters of such fluid). That substitution fluidand the fluid accumulated by the patient in between treatments isultrafiltered over the course of the HF treatment, providing aconvective transport mechanism that is particularly beneficial inremoving middle and large molecules waste products.

Hemodiafiltration (“HDF”) is another blood treatment modality thatcombines convective and diffusive clearances. HDF uses dialysate to flowthrough a dialyzer, similar to standard hemodialysis, providingdiffusive clearance. In addition, substitution solution is provideddirectly to the extracorporeal circuit, providing convective clearance.

Peritoneal dialysis uses a dialysis solution, also called dialysate,which is infused into a patient's peritoneal cavity via a catheter. Thedialysate contacts the peritoneal membrane of the peritoneal cavity.Waste, toxins and excess water pass from the patient's bloodstream,through the peritoneal membrane, and into the dialysate due to diffusionand osmosis, i.e., an osmotic gradient occurs across the membrane. Thespent dialysate is drained from the patient, removing waste, toxins andexcess water from the patient. This cycle is repeated.

There are various types of peritoneal dialysis therapies, includingcontinuous ambulatory peritoneal dialysis (“CAPD”), automated peritonealdialysis (“APD”), tidal flow APD and continuous flow peritoneal dialysis(“CFPD”). CAPD is a manual dialysis treatment. The patient manuallyconnects an implanted catheter to a drain, allowing spent dialysatefluid to drain from the peritoneal cavity. The patient then connects thecatheter to a bag of fresh dialysate, infusing fresh dialysate throughthe catheter and into the patient. The patient disconnects the catheterfrom the fresh dialysate bag and allows the dialysate to dwell withinthe peritoneal cavity, wherein the transfer of waste, toxins and excesswater takes place. After a dwell period, the patient repeats the manualdialysis procedure, for example, four times per day, each treatmentlasting about an hour. Manual peritoneal dialysis requires a significantamount of time and effort from the patient, leaving ample room forimprovement.

Automated peritoneal dialysis (“APD”) is similar to CAPD in that thedialysis treatment includes drain, fill, and dwell cycles. APD machines,however, perform the cycles automatically, typically while the patientsleeps. APD machines free patients from having to manually perform thetreatment cycles and from having to transport supplies during the day.APD machines connect fluidly to an implanted catheter, to a source orbag of fresh dialysate and to a fluid drain. APD machines pump freshdialysate from the dialysate source, through the catheter, into thepatient's peritoneal cavity, and allow the dialysate to dwell within thecavity, causing the transfer of waste, toxins and excess water to takeplace. The source can be multiple sterile dialysate solution bags.

APD machines pump spent dialysate from the peritoneal cavity, though thecatheter, to the drain. As with the manual process, several drain, filland dwell cycles occur during APD. A “last fill” occurs at the end ofCAPD and APD, which remains in the peritoneal cavity of the patientuntil the next treatment.

Both CAPD and APD are batch type systems that send spent dialysis fluidto a drain. Tidal flow systems are modified batch systems. With tidalflow, instead of removing all of the fluid from the patient over alonger period of time, a portion of the fluid is removed and replacedafter smaller increments of time.

Continuous flow, or CFPD, systems clean or regenerate spent dialysateinstead of discarding it. The systems pump fluid into and out of thepatient, through a loop. Dialysate flows into the peritoneal cavitythrough one catheter lumen and out another catheter lumen. The fluidexiting the patient passes through a reconstitution device that removeswaste from the dialysate, e.g., via a urea removal column that employsurease to enzymatically convert urea into ammonia. The ammonia is thenremoved from the dialysate by adsorption prior to reintroduction of thedialysate into the peritoneal cavity. Additional sensors are employed tomonitor the removal of ammonia. CFPD systems are typically morecomplicated than batch systems.

In each of the kidney failure treatment systems discussed above, it isimportant to control ultrafiltration, which is the process by whichwater (with electrolytes) moves across a membrane, such as a dialyzer orperitoneal membrane. For example, ultrafiltration in HD is a result oftransmembrane and osmotic pressure differences between blood anddialysate across a dialyzer membrane. For a given osmotic pressure, thegreater the transmembrane pressure the more rapid the ultrafiltration.

Many of the above-described dialysis systems employ a pumping cassette.The pumping cassette typically includes a flexible membrane that ismoved mechanically to push and pull dialysis fluid out of and into,respectively, the cassette. Certain known systems include flexiblesheeting on one side of the cassette, while others include sheeting onboth sides of the cassette. Positive and/or negative pressure can beused to operate the pumping cassettes.

The pumping cassettes have many design concerns. For example, oneproblem with the pumping cassettes is leakage. If the flexible membranesexperience a pinhole or tear, fluid and air can move from one side ofthe membrane to the other. Movement of fluid from inside the cassette tothe inner workings of the machine can damage the machine. Movement ofair from the machine into the cassette can compromise the sterility ofthe fluid pathways defined by the cassette.

Another problem with cassette-based pumping occurs when the cassette isloaded improperly into the machine. Proper alignment is importantbecause portions of the flexible membrane must match correspondingmachine portions, e.g., pump and valve actuators. Improper loading canlead to undue mechanical stress being placed on the cassette, harmingpotentially the cassette and/or the actuator. Improper cassette loadingcan also degrade or prohibit performance of the system.

A further dilemma, especially in CFPD, is the coordination of multiplefluid deliveries. Cassette-based peritoneal pumping systems thatadminister fluids continuously to patients are required to withdrawfluid (ultrafiltrate) from and add fluid (concentrate) to a continuouslyflowing dialysis fluid loop. The additional fluids have typicallynecessitated additional dedicated pumps, which make the cassette anddialysis machine larger and noisier. Scheduling the operation ofmultiple pumps also presents a challenge to system implementers.

Yet another problem associated with cassette-based pumping is theentrapment of air or other gas in the fluid pathways. Air can enter thesystem via leaking connections, improper priming, faulty tubing andfaulty cassettes. Patient therapy also produces various gases that enterthe system. Cassette-based pumps are designed to pump fluid, not gas.Moreover, the removal and delivery of fluid from and to the patientneeds to be monitored and controlled. For PD-type systems, air and gasesupset volume measurement systems that assume no air or gas exists in thefluid pathways. Air and gases can also be uncomfortable for the patientand impede proper waste removal. For HD-type systems, air in the bloodstream can be harmful to the patient.

Cost, ease of manufacturing, durability and reliability are additionalconcerns facing cassette-based dialysis systems. A need therefore existsfor improved cassettes for cassette-based dialysis systems, whichsatisfy the above-described concerns.

SUMMARY

The examples described herein disclose dialysis systems employing aflexible pumping cassette such as: hemodialysis (“HD”), hemofiltration(“HF”), hemodiafiltration (“HDF”), peritoneal dialysis ((“PD”),including continuous ambulatory peritoneal dialysis (“CAPD”), automatedperitoneal dialysis (“APD”), tidal flow APD and continuous flowperitoneal dialysis (“CFPD”) modalities). The systems may also be usedin any type of continuous renal replacement therapy (“CRRT”). Theexamples below include a diffusion membrane or filter, such as adialyzer, e.g., for HD or HDF, a hemofilter, e.g., for HF or thepatient's peritoneum, e.g., for PD. Moreover, each of the systemsdescribed herein may be used in clinical or home settings. For example,the systems may be employed in an in-center HD machine, which runsvirtually continuously throughout the day. Alternatively, the systemsmay be used in a home PD machine, which is typically run at night whilethe patient is sleeping. One particularly suitable therapy for theembodiments described herein is home hemodialysis (“HHD”) and inparticular high convection home hemodialysis (“HCHD”).

The examples below include a dialysate (replacement fluid) supply, whichcan be multiple bags of dialysate supply that are ganged together andused one after another. Further alternatively, each of the systems shownbelow can be used with an online dialysate source, such as one or moreconcentrate pump configured to combine one or more concentrate withwater to form dialysate online. Online sources are used commonly within-center HD systems for example. While the systems are described hereinfor use with dialysate, it is expressly contemplated to use the flexiblesheeting cassettes and other apparatus with other medical fluids, suchas saline, lactated ringers, drugs and/or blood.

Various flexible sheeting cassettes are shown and described herein. Theflexible sheeting cassettes use a multitude of flexible sheets that arewelded, heat sealed, adhered, chemically bonded, folded or otherwiseformed together at desired places to produce fluid flow paths, fluidheating pathways, peristaltic pump paths, volumetric pumping areas,balance chambers (matched flow equalizers) and any combination thereof.The different sheets can be formed as separate sheets before attachingthem together or be a single sheet that is folded one or more time toproduce the different layers. The sheets provide an economical andreadily producible alternative to known medical fluid pumping cassettes,which typically include a hard plastic component and one or moreflexible sheet sealed to the hard plastic component.

It is expressly contemplated however to provide a cassette in which somecomponents use a hard plastic member and others use flexible sheetsonly. For example, it may be advantageous to form the valves and certainpathways using a hard plastic piece in combination with one or moreflexible sheet and form the pumping portion(s), balance chamber(s)and/or heating fluid pathway using flexible sheets only. Certainembodiments shown below combine flexible sheet cassettes with tubingloops, for example, tubing loops used in combination with a peristalticpump roller. It is also expressly contemplated to provide a cassette inwhich the flow paths, heating pathway, pumping portion and volumecontrol portion are each formed using flexible sheeting, but whichincludes a rigid frame for ease of handling, loading, etc.

In one embodiment a cassette is shown using two or three sheeting layersas needed to provide fluid pathways, a peristaltic pumping portion, abalance chamber portion, which are sealed together and formed withconnectors that connect to one or more supply bag, a drain bag and apatient (as used herein, “patient” generally refers to a patient'speritoneum, a dialyzer, a hemofilter, a extracorporeal circuit and anycombination thereof). In one implementation, a separate fluid heatingpathway is provided and connected fluidly to the flexible sheetingcassette via separate tubes.

In another embodiment, the fluid heating pathway is formed using thesame sheets that form other components of the dialysate fluid system,such as volumetric pump portions. The volumetric or membrane pumpingportions pump a known volume of fluid with each stroke and thereforepreclude the need for separate match flow equalizers or balancechambers.

Any of the flexible sheeting cassettes described herein can have one ormore pumping portion. For example, the flexible sheeting cassettes canform multiple peristaltic pumping portions in combination with multiplebalance chambers, which operate to produce an at least substantiallysteady flow of fresh and spent dialysate to the “patient” and drain,respectively. In another example, the flexible sheeting cassettes canform multiple volumetric or membrane pumping portions.

The flexible sheeting membranes also incorporate a vent, which can belocated advantageously just down stream of an integrated or separatefluid heating pathway. This configuration enables air or gas generatedvia the heating to be vented or released to atmosphere. The vent forexample can be located at the top of a vertically disposed or positionedcassette to allow for automatic air purging. Or, the cassette can bemounted horizontally in the machine and operate with a valve, whichopens when air is detected. The System could vent/release gas/air toother parts of the disposable (such as a solution bag or drain line),not just to the atmosphere.

In an embodiment the flexible sheeting cassettes include connectors thatconnect the tubes that lead to fluid bags, the patient, a dialyzer,extracorporeal circuit, etc. In an embodiment the connectors include abody, which can be rigid, and which is sealed between two of theflexible sheets. One or both of the flexible sheets can have athermoformed flow path, which is sealed to the other flexible sheet toform a closed flow path that leads from the connector body to a desireddestination within the flexible sheeting cassette. An external end ofthe connector body can include a luered or ferruled end, which isconfigured to be sealed tightly to a tube running from the flexiblesheeting cassette.

In an embodiment one of the flexible sheets includes a substantiallycircular thermoformed pathway leading to inlet and outlet pump pathways.A peristaltic pump roller or actuator operates with the substantiallycircular fluid pathway to form an integral peristaltic pumping portionof the flexible sheeting cassette. As discussed above, one or more suchpumping portions may be provided in any single cassette. In such a case,described below are two embodiments for using a single roller to drivetwo different peristaltic pumping pathways. In one example, the flexiblesheeting cassette is folded over a member, causing two inwardly facingperistaltic pumping portions to be coupled operably to a singleperistaltic pump roller. In a second example, the peristaltic pumpingpathway is a semicircle as opposed to a substantially complete circle,wherein two of the semicircular flow paths operate with the sameperistaltic pump roller, to drive two different fluids through twodifferent pathways.

Multiple embodiments for producing match flow equalizers or balancechambers using multiple flexible sheets are also disclosed herein. Inone implementation, three sheets are used to create upper and lowerbalance chamber compartments, namely, one between an upper sheet and amiddle sheet and the other compartment between the middle sheet and alower sheet. Each compartment can have single or multiple fluid pathwaysleading to and from such compartment. Pumping fluid into a compartmentdispenses a like amount of fluid from the other compartment and viseversa. In an embodiment, each compartment includes two pathwaysconnected thereto, wherein one pathway is an inlet pathway to thecompartment and the other pathway is an outlet pathway from thecompartment. In another implementation, only a single pathwaycommunicates with each of the compartments, causing fluid entering andexiting each compartment to flow through the same single pathway.

In an alternative embodiment, two flexible sheets are formed with arigid, e.g., spherical plastic chamber to form a balance chamber. Here,one compartment is formed between the rigid chamber and an upperflexible sheet. The second compartment is formed between the twoflexible sheets. A rigid plate or backing is abutted against the lowerflexible sheet, causing the upper flexible sheet to have only onedirection in which to move when the lower compartment is filled. Whenthe lower compartment is filled the upper flexible sheet is movedupwards towards an inner wall of the rigid chamber to dispense fluidfrom the upper compartment. Next fluid is filled into the uppercompartment, pushing the upper sheet down towards the lower sheet todispense fluid from the lower compartment.

In yet another alternative balance chamber embodiment, a plurality offlexible sheets is formed with a plurality of balance chamber tubes toform the balance chamber. The tubes act as fluid inlets and fluidoutlets, which alternatively are formed via thermo-forming one or bothof the flexible sheets. Again, each balance chamber compartment caninclude a single inlet/out tube or multiple dedicated inlet/outlet tubesto produce a single fluid inlet/outlet or separate fluid inlet/outlet.

The balance chambers are generally described herein operating withpumps, such as peristaltic pumps. In an alternative embodiment describedbelow, the balance chamber is placed inside a magnetic field. Hence, themembrane (e.g., inner membrane) of the balance chamber that is drivenback and forth within the chamber is doped or otherwise coupled with aferromagnetic material. For example, a thin carbon layer can besandwiched between outer flexible layers of air insert medical gradematerial. The magnetic field is modulated or polarized to move theimpregnated membrane. A controller within the dialysis unit powerselectromagnets located at either side of the balance chambersequentially to draw the magnetic inner membrane to one side of thechamber and then the other, dispelling and drawing in fluid with eachhalf-stroke. In this manner, the balance chamber (or dual balancechambers) is itself driven as opposed to being driven by a separatepump, eliminating the need for the second pump. As described below, thebalance chamber systems sometimes use an ultrafiltration (“UF”) meter,which is also typically passive or non-self driving. The UF meter canalso be driven magnetically as described herein. Alternately, one of themagnetically driven balance chambers drives the UF meter. As furtherdiscussed below, volumetric pumps may also be modified to be drivenmagnetically.

As shown below an integrated volumetric or membrane pump can be formedusing two flexible sheets and upper and lower chambers defined by themachine in which the cassette is loaded. The machine is configured topull a vacuum on each of the separate sheets to pull the sheets towardthe chamber wall and to provide positive pressure to push the sheettowards the opposing chamber wall as needed to draw in or push outfluid. A fluid-in pathway and fluid-out pathway communicate fluidly withthe space between the flexible sheets.

The inlet and outlet pathways are valved to enable fluid to be pulledinto the volumetric pump chamber in one step and to be pushed out thevolumetric pump chamber in a second step. As shown below, to pull fluidinto volumetric pump chamber, positive pressure is removed and negativepressure is applied to the outer surface of one the flexible sheets topull it from the other flexible sheet (which is under negative pressurefrom the other side of the chamber) towards its vacuum source, causingthe pumping chamber between the sheets to open, create a vacuum andthereby pull fluid into the chamber. Next, positive pressure is appliedto one of the sheets, pushing the flexible membranes closed and fluidout the pump outlet pathway.

Multiple embodiments are discussed herein for forming an integratedfluid heating pathway. The pathway can be a thermoformed pathway in onesheet that is bonded to a second sheet. In another embodiment, threesheets are used, wherein upper and lower pathways are formed with a flatmiddle sheet. In any of the embodiments described herein, the middlesheet includes one or more aperture to enable fluid, for example, totravel from an upper fluid heating pathway to a lower fluid heatingpathway. Or with respect to the balance chambers, an aperture in themiddle flexible membrane enables fluid exiting one (upper or lower)compartment to be combined with fluid exiting the other compartment in asingle flow path.

Various embodiments are described herein for selectively forming theseals between two of three abutting sheets and for sealing three sheetsto together. For example, a pattern of curable adhesive can be providedon one or more sides of the middle sheet to enable one or more outersheets to be selectively adhered and sealed thereto. Alternatively, theenergy provided by a heating die can be varied such that the heatgenerated by the die is set to seal only two of three sheets together orto seal all three sheets together.

As discussed above, any of the flexible sheeting cassettes can include arigid component, which for example can include flow pathways, valveseats, rigid balance chamber portions, etc. As shown below, that rigidportion can be made to communicate with an all-flexible portion, whichforms the remaining components of the cassette.

As discussed above, the peristaltic pumping portions can alternativelybe tubes that are connected fluidly to a flexible sheeting cassette,which can include a heater flow path, balance chamber portion(s) andassociated flow paths and valve seats.

In one embodiment one flexible sheeting cassette is provided for thedialysate portion of an HD, HF or HDF system, wherein a second bloodcassette is provided. Both cassettes are loaded into the same machine inone embodiment. Alternatively, blood and dialysate portions of an HD, HFor HDF system can be formed in the same cassette.

It is therefore an advantage of the present disclosure to provideimproved dialysis systems.

It is another advantage of the present disclosure to provide improveddialysis cassettes.

It is a further advantage of the present disclosure to provide improvedhome dialysis therapies.

It is still another advantage of the present disclosure to incorporateperistaltic pumping portions into a cassette formed from multipleflexible sheets.

It is still a further advantage of the present disclosure to incorporatemembrane or volumetric pumping portions into a cassette formed frommultiple flexible sheets.

It is a further advantage of the present disclosure to provide multipleways to form fluid pathways in two or three abutting flexible membranes.

It is yet another advantage of the present disclosure to incorporatebalance chamber portions into a cassette formed from multiple flexiblesheets.

It is yet a further advantage of the present disclosure to provide arelatively low cost flexible sheeting cassette.

Moreover, it is an advantage of the present disclosure to providemethods for selectively sealing two of three abutting sheets or three ofthree abutting sheets together, for example.

Still additionally, it is an advantage of the present disclosure toprovide a magnetically driven volumetric balancing or pumping device.

Additional features and advantages of the present disclosure will beapparent from, the following Detailed Description of the Invention andthe figures.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a schematic view of one embodiment of a cassette-baseddialysis system employing a flexible sheeting cassette having aperistaltic pumping portion, a single balancing chamber volumetriccontrol portion and an external heater bag.

FIG. 2 is a schematic view of one embodiment of a cassette-baseddialysis system employing a flexible sheeting cassette having avolumetric or membrane pumping portion and an inline heating portion.

FIG. 3 is a schematic view of one embodiment of a cassette-baseddialysis system employing a flexible sheeting cassette having dualperistaltic pumping portions, dual balancing chamber portions and anexternal heater bag.

FIG. 4 is a sectioned perspective view of Detail IV shown in FIG. 1,which highlights one embodiment of an inlet/outlet connector portion ofthe flexible sheeting cassettes.

FIG. 5 is a sectioned perspective view of Detail V shown in FIG. 1,which highlights one embodiment of a peristaltic portion for theflexible sheeting cassettes.

FIG. 6 is a sectioned perspective view of Detail VI shown in FIG. 1,which highlights one embodiment of a balancing chamber portion for theflexible sheeting cassettes.

FIG. 7 is a sectioned elevation view taken along line VII-VII of FIG. 6,illustrating the balancing chamber portion of the flexible sheetingcassette in operation with a dialysis machine.

FIG. 8 is a sectioned view taken along line VIII-VIII of FIG. 6, whichshows upper and lower fluid pathways leading to the balancing chamberportion of the flexible sheeting cassette shown in FIG. 6.

FIGS. 9A to 9C are sectioned elevation views of Detail IX shown in FIG.2, illustrating different valve states of a pump cycle for a volumetricpumping operating using the flexible sheeting cassettes.

FIG. 10A is a sectioned perspective view of Detail X shown in FIG. 2,which highlights one embodiment for an inline heater portion of theflexible sheeting cassettes.

FIG. 10B is a sectioned elevation view of a bi-level inline heaterportion in operation with a dialysate fluid heater.

FIG. 11 is a perspective view of Detail XI shown in FIG. 2, illustratingone embodiment of an inline air vent portion for the flexible sheetingcassettes.

FIG. 12A is a sectioned elevation view illustrating one embodiment forconfiguring a single peristaltic pump actuator to drive fluid throughtwo different flow paths of the flexible sheeting cassettes.

FIG. 12B is a plan view illustrating another embodiment for configuringa single peristaltic pump actuator to drive fluid through two differentflow paths of the flexible sheeting cassettes.

FIG. 13 is a sectioned perspective view illustrating one embodiment ofthe flexible sheeting cassettes employing a pressure (or otherparameter) sensing area in combination with a pressure (or otherparameter) sensor.

FIG. 14 is a sectioned perspective view of the flexible sheetingcassettes showing one method and resulting apparatus for selectivelysealing three flexible sheets together.

FIG. 15 is a perspective view of an example flexible sheeting cassetteshowing a second method and resulting apparatus for selectively sealingthree flexible sheets together.

FIG. 16 is an elevation view of a portion of a flexible sheetingcassette illustrating a third method for selectively sealing threeflexible sheets together.

FIG. 17 is a perspective view of one embodiment for an overall cassettewhich combines path forming flexible sheets with a rigid cassetteportion.

FIG. 18 illustrates one embodiment for configuring a cassette having aflexible sheeting portion and a rigid portion with corresponding valveactuation, pump actuation and heater.

FIGS. 19A and 19B are sectioned elevation views showing anotherembodiment for a balancing chamber portion using two flexible sheets incombination with a rigid plastic domed component.

FIGS. 20A to 20D are perspective views in various stages of manufactureof a further alternative embodiment of a balance chamber portionproduced via multiple flexible sheets.

FIGS. 21A to 21G are various views of one system employing a flexiblesheeting dialysate cassette in combination with a separate blood-sidecassette.

FIGS. 22A to 22D are perspective views of a further alternative systememploying a flexible sheeting dialysate cassette in combination with aseparate blood-side cassette.

FIG. 23 is a perspective view of yet another alternative medical fluidcassette for use with a system employing a gravimetric volume controlmethodology.

FIGS. 24A and 24B are perspective views of an alternative flexiblesheeting cassette system in which the machine includes clamping membersthat compressively form pump, flow and fluid heating paths.

FIG. 25A is a schematic view of a fluid heating pathway formed viacompressive clamping and a fluid heater operable with the compressedfluid heating pathway.

FIG. 25B is a perspective view of a separate heater bag with a fluidheating pathway formed via mechanical compression and a separate heaterfor the heater bag.

FIGS. 26A and 26B show a balance chamber portion of the disposablecassette formed via mechanical clamping and also illustrate a magneticfield that is used to drive the balance chamber.

FIG. 27 illustrates a balancing tube or balancing piston driven by amagnetic field.

FIG. 28 illustrates a volumetric pump driven by a magnetic field.

DETAILED DESCRIPTION

The examples described herein are applicable to any medical fluid (suchas dialysate, substitution fluid and blood) therapy system requiring adisposable fluid pumping cassette. The systems are particularly wellsuited for the control of kidney failure therapies, such as all forms ofhemodialysis (“HD”) including (“HHD”), hemofiltration (“HF”),hemodiafiltration (“HDF”), peritoneal dialysis (“PD,” includingcontinuous ambulatory peritoneal dialysis (“CAPD”), automated peritonealdialysis (“APD”), tidal flow APD and continuous flow peritoneal dialysis(“CFPD”) modalities). The systems may also be used in any type ofcontinuous renal replacement therapy (“CRRT”).

The examples below include a diffusion membrane or filter, such as adialyzer, e.g., for HD or HDF, a hemofilter, e.g., for HF or aperitoneum, e.g., for PD. Certain examples show a cassette with a singlepatient inlet and outlet, e.g., for batch type CAPD or APD. Dialysate inCAPD and APD is typically delivered to the patient, allowed to dwell fora period, and then pumped from the patient and discarded to drain. Thosecycles are then repeated a number of times. The to- and from-patientlines are teed together and valved appropriately, for example, so thatdialysate can be delivered and removed at different times via the samesingle line and connection to and from the patient.

Other systems include a dialysate inlet and a dialysate outlet, e.g.,for a dialyzer or hemofilter used with HD, HDF or HF. The systems mayeach also be modified for use with a single or dual catheter as the casemay be. CFPD typically uses a dual lumen catheter and thus requiresseparate inlets and outlets as well.

Moreover, each of the cassette-based systems described herein may beused in clinical or home settings. For example, the systems may beemployed in an in-center HD machine, which runs virtually continuouslythroughout the day. Alternatively, the systems may be used in a home PDmachine, which is typically run at night while the patient is sleeping.Home hemodialysis (“HHD”) (including high convection home hemodialysis(“HCHD”)) machines are also one preferred type of therapy machine foruse with the embodiments described herein.

The examples below include a dialysate (or replacement fluid) supply,which for convenience is shown as multiple bags of the fluid.Alternatively, a single bag of dialysate supply is used. Furtheralternatively, each of the systems shown below can be used with anonline dialysate or replacement fluid source, such as one or moreconcentrate pump configured to combine one or more concentrate withwater to form dialysate online. For example, online sources are usedcommonly with HD systems.

Each of the systems shown herein operates with a heater that heats thedialysate or replacement fluid to a desired temperature. The heaters canbe inline heaters located upstream or downstream of the fresh supplypump. The systems may alternatively operate with a batch type heaterand/or a heater located upstream of the pump.

The systems also include a cassette with an inline air removal device(e.g., hydrophobic vent). Alternatively, a batch-type air removaldevice, such as an air trap is used. The air removal device can belocated at or near the heating pathway to capture air that has egressedfrom the solution due to heating.

The flow schematics shown herein mainly involve the dialysate orreplacement fluid portion of the kidney failure machine. HD, HF and HDFmachines also include blood pumping systems. Various examples of bloodcassettes are also discussed below.

HD, HF and HDF also include dialysate proportioning systems, mentionedabove, which are also known and need not be described here. U.S. Pat.No. 5,247,434 (“the '434 Patent”), assigned to the assignee of thepresent application, the entire contents of which are incorporatedexpressly herein by reference, describes one example of a suitableproportioning system.

Referring now to the drawings and in particular to FIG. 1, oneembodiment of a system employing a flexible sheeting cassette 10 a isillustrated by system 10. System 100 a is advantageous in one respectbecause it employs a peristaltic pump 30 in combination with avolumetric balancing device or balance chamber. Peristaltic pumps, suchas pump 30, are typically used to pump clean or sterile fluids, such asdialysate or replacement fluid, because the pump hardware does notcontact and thus contaminate the fluid. The only part of the pump incontact with the dialysate/replacement fluid is the peristaltic pumpingpath or tube segments, which are sterilized before therapy. Also,because peristaltic pumps include no moving parts in contact with thedialysate/replacement fluid, the pumps are relatively inexpensive.Peristaltic pumps also lack the valves, seals and glands used in othertypes of pumps, which makes pump 30 for example, comparativelyinexpensive and easy to maintain.

The volumetric balancing of system 100 a uses first and second chambersof substantially equal volume in one embodiment. Each chamber includestwo compartments, one termed a “pre-dialyzer” compartment and the othera “post-dialyzer” compartment. Each opposing “pre” and “post”compartment of a chamber is separated by a flexible diaphragm.Solenoid-actuated valves control the filling and emptying of eachcompartment. In general, each compartment is completely filled beforeits contents are discharged. Also, the “pre” compartments arealternately filled and discharged and the “post” compartments arealternately filled and discharged. Filling a “pre” compartment causes adischarge of a corresponding and opposing “post” compartment,respectively. Filling a “post” compartment causes a discharge of acorresponding and opposing “post” compartment.

Since the volumes of opposing “pre” and “post” compartments of the twochambers are equal, the system volumetrically balances the flow ofdialysate to and from the dialyzer. One benefit of this volumetricallycontrolled system is that dialysate flow to the dialyzer can beaccurately measured over a wide range of flowrates.

System 100 a includes a plurality of supply bags 12 a to 12 c. Thedialysate supply to system 100 a is alternatively any of the systemsdescribed above, such as an online supply. System 100 a also includes aninitial drain bag 14 in the illustrated embodiment. With PD for examplethe patient's peritoneum is full of spent dialysate at the beginning oftherapy. That spent dialysate is from a last-fill from the previousnight's therapy. The first step in the treatment in PD is therefore todrain the spent dialysate to drain bag 14. Thereafter, supply dialysateis pumped from supply bags 12 a to 12 c through cassette 10 a to thepatient (as used herein, “patient” refers to a dialyzer, anextracorporeal circuit, a patient's peritoneum or a combination thereofdepending on the therapy involved). Those supply bags then double asdrain bags over the different cycles of treatment, e.g., after thedialysate has dwelled inside the patient's peritoneum for a designatedamount of time and is thereafter pumped back through the cassette to thedrain bag. For example, dialysate could be pumped initially from supplybag 12 a, through cassette 10 a, to the patient. After a preset dwellperiod, the spent dialysate is then pumped from the patient, throughcassette 10 a to bag 12 a, which is now a drain bag. Afterwards, system100 a in a next cycle pumps fresh dialysate from supply bag 12 b to thepatient, and so on.

Supply bags 12 a to 12 c are connected fluidly to supply connectors 16 ato 16 c via supply tubes 18 a to 18 c, respectively. Supply connectors16 a to 16 c are connected sealingly to flexible sheeting cassette 10 aas illustrated in more detail below in connection with FIG. 4. Drain bag14 is connected fluidly to drain connector 22 via drainline 24. Drainconnector 22 is connected sealingly to flexible sheeting cassette 10 ain the same manner that supply connectors 16 a to 16 c are connectedsealingly to flexible sheeting cassette 10 a as shown in more detailbelow in connection with FIG. 4.

Flexible sheeting cassette 10 a defines or includes flow paths 26 a to26 d that enable fluid flowing through lines or tubes 18 a to 18 c and24 to communicate fluidly with a peristaltic pumping portion 30, whichflexible sheeting cassette 10 a also defines or includes. Peristalticpumping portion 30 is shown in more detail below in connection with FIG.5. Peristaltic pump portion 30 operates with a peristaltic pump actuatorlocated in the dialysis machine. Each of the flow paths 26 a to 26 ddefined by flexible sheeting cassette 10 a includes or defines a valvecontact portion 28 a to 28 d, respectively. Flow paths 26 a to 26 d andrespective valve contact portions 28 a to 28 d are shown in more detailbelow in connection with FIG. 4.

In system 100 a, fluid from one of the supply bags 12 a to 12 c ispumped through peristaltic pump portion 30, through a pump outletpathway 32, through a to-heater pathway 34 a, through a to-heaterconnector 36 a, through an external to-heater tube 38 a and finally toan external inline heater 40, which includes a fluid heating pathway 42a. To- and from-heater connectors 36 a and 36 b are sealed to flexiblesheeting cassette 10 a in the same manner in one embodiment as areconnectors 16 a to 16 c and 22 shown in detail below in connection withFIG. 4.

External heater bag 40 defines a serpentine fluid heating pathway 42 a,through which the fluid or dialysate travels. As the fluid or dialysatetravels through the fluid heating pathway 42 a, a plate, convective,radiant, inductive or other type of heater is used alone or incombination to heat the fluid. The heater heating the fluid flowingthrough heating pathway 42 a can be located external to the dialysismachine that houses flexible sheeting cassette 10 a or can be integratedinto such machine. As seen in FIG. 2, a fluid heating pathway 42 b isintegrated alternatively into a flexible sheeting cassette 10 b. Oneexample of a fluid heating pathway is shown in more detail below inconnection with FIG. 10A. FIG. 10B shows a two sided fluid heatingpathway operating with a fluid heater.

Heated dialysate fluid flows from inline heater 40, through an externalfrom-heater line or tube 38 b, through a from-heater connector 36 b ofcassette 10 a, through a from-heater pathway 34 b defined by flexiblesheeting cassette 10 a, and to the volumetric control portion ofcassette 10 a, which is described in more detail below. To- andfrom-heating pathways 34 a and 34 b each define or include a valvecontact portion 28 e and 28 f, respectively. Examples of valve contactportions are shown in more detail below by valve contact portions 28 ato 28 d of FIG. 4.

It should be appreciated that valve contact portions 28 e and 28 f areopen when fluid is pumped to the patient, so that such fluid ordialysate can be heated. When fluid is pulled from the patient andpumped to drain, associated valve actuators close lines 34 a and 34 b atvalve contact portions 28 e and 28 f. In the drain cycle, a valveactuator operates with valve contact portion 28 g defined by or includedin pump outlet pathway 32 to open pathway 32. In this manner, the heaterand associated pathways and lines are bypassed during drain.

The materials used for supply bags 12 a to 12 c and drain bag 14 can beany suitable medical grade material, such as polyvinyl chloride (“PVC”),e.g., monolayer PVC films, non-DEHP PVC monolayer film, multilayernon-PVC films (wherein different layers are chosen to provide strength,weldability, abrasion resistance and minimal “sticktion” to othermaterials such as rigid cassette materials), polypropylene/polyethyleneblend, polypropylene or Kraton blend, coextruded or laminated, with orwithout gas barrier, polyester, polyolefin, ULDPE. The materials usedfor external lines or tubes 18 a to 18 c, 24, 38 a and 38 b can be anysuitable medical grade tubing material, such as PVC, non-DEHP PVC,polybutadiene (“PB”), ethylene vinyl acetate (“EVA”), polypropylene(“PP”) blend, polyethylene (“PE”) blend, Kraton blend and polyolefinblends. The materials used for external fluid heater bag 40 includingfluid pathway 42 a include PVC, PP/kraton blend.

The dialysis unit or machine (examples shown below in connection withFIGS. 21G and 22A) operating with flexible membrane cassette 10 aincludes an apparatus configured to detect air in the dialysate flowpath. One highly suitable place to detect air or other gas bubbles inthe system is at a point in the flow path just downstream of fluidheater 40. The heat from the heater causes air or other gas to egressfrom solution. Accordingly, an air detection sensor is positioned tooperate with from-heater pathway 34 b in one embodiment. Suitable airdetectors are disclosed in the parent application of the presentdisclosure.

Valve actuators of cassettes 10 a with valve contact portions 28 h and28 i enable dialysate to be directed desirably and alternatively toeither an inline vent 44 or to a volumetric balancing device orbalancing chamber 50. If air is detected in the system, the valveactuator operating with valve contact portion 28 i is closed, while thevalve actuator operating with valve contact portion 28 h is opened,allowing the fluid to reach vent 44, so that any air entrained in thefluid can escape from system 100 a. One embodiment for vent 44 is shownin more detail below in connection with FIG. 11. Once the air is purgedfrom flexible sheet 10 a, the valve actuator operating with valvecontact portion 28 h is closed, while the valve actuator operating incombination with valve contact portion 28 i is opened, allowing thepurged dialysate to flow to balance chamber 50.

In an alternative embodiment cassette 10 a is mounted vertically in themachine with vent 44 located at the top of the mounted cassette, suchthat any air in from-heater pathway 34 b escapes automatically from vent44. Here, separate valve actuators and valve seats 28 h and 28 i are notneeded. Further if, vent 44 is pointed upwardly, separate valveactuators and valve seats 28 h and 28 i are not needed even if cassette10 a is mounted horizontally in the machine.

In an alternative embodiment, air in flexible sheeting cassette 10 a ispumped to heater bag 40 or to drain bag 14. For example, air can beallowed to collect at the top of heater bag 40, which is laidhorizontally on a heater plate in one implementation. If air is detecteddownstream of heater bag 40, appropriate valve seats 28 are switched sothat the fluid is pumped to drain until no more air is detected.

Balance chamber 50 of the flexible sheeting cassette 10 a (and othercomponents discussed herein) includes three plies or flexible sheets inone embodiment. One embodiment of balance chamber 50 is shown below inconnection with FIGS. 6 to 8, which will be discussed in more detailbelow. The three plies are sealed in a circular arrangement 52 in oneembodiment to form upper and lower fluid compartments 54 a and 54 b(seen best in FIG. 7). Fluid pumped through pump outlet pathway 32 flowseventually through balance chamber inlet pathways 56 a or 56 b asdetermined selectively by valve actuators operating with valve contactportions 28 j or 28 k, respectively. In the embodiment illustrated inconnection with FIGS. 6 to 8, balance chamber inlet pathway 56 a is influid communication with upper compartment 54 a of balance chamber 50,while balance chamber inlet pathway 56 b is in fluid communication withlower balance chamber compartment 54 b. As described in more detailbelow, fluid flows from compartments 54 a and 54 b, through balancechamber outlet pathways 58 a and 58 b as determined selectively byactuators operating with valve contact portions 28 l and 28 m,respectively.

Fluid that flows through balance chamber outlet pathways 58 a or 58 bflows into a to-patient pathway 60 a as seen in FIG. 1. FIGS. 6 and 8show one embodiment for how fluid flowing through separate balancechamber outlet pathways 58 a and 58 b eventually tees together into asingle to-patient pathway 60 a.

The illustrated system 100 a of FIG. 1 can be used with APD, tidal flowPD, or CAPD, for example, which typically uses a single connection tothe patient for batch-type fill and drain cycles. In such a case,to-patient pathway 60 a also serves as a from-patient pathway thatcommunicates with connector 62 a. To perform a drain cycle, connector 62a becomes a from-patient connector, to-patient pathway 60 a becomes afrom-patient pathway, outlet pathways 58 a and 58 b to the balancechamber compartments become inlets, and the previously described inlets56 a and 56 b at the balance chamber compartments become balance chamberoutlets. The peristaltic pump operating with peristaltic pump portion 30of cassette 10 a is run in reverse, pulling spent dialysate from thepatient's peritoneum, through balance chamber 50 and associated pathwaysand thereafter pushing the spent dialysate to a drain bag, house drainor other appropriate drain.

It is, however, possible to use system 100 a in a hemodialysistreatment, which typically includes a dialyzer having a dialysate inletand a dialysate outlet (not illustrated). Or system 100 a could also beused with a PD system employing a dual lumen catheter. Here, a separatefrom-patient pathway 60 b is teed into to-patient pathway 60 a. Aseparate from-patient connector 62 b is provided and placed in fluidcommunication with from-patient pathway 60 b. Connectors 62 a and 62 bare fixed to flexible sheeting cassette 10 a via the same apparatus andtechnique shown for example with connectors 16 a to 16 c and 22 in FIG.4. Valve actuators are configured to operate with valve contact portions28 n and 28 o to selectively allow fluid to flow either out to-patientconnector 62 a or in through from-patient connector 62 b, respectively.To pump fluid out of cassette 10 a to the patient or dialyzer, the valveactuator operating with valve contact portion 28 o is closed, while thevalve actuator operating with valve contact portion 28 n is opened. Topump fluid into cassette 28 a, the valve actuator operating with valvecontact portion 28 n is closed, while the valve actuator operating withcontact portion 28 o is opened.

Whether a single connector 62 a is provided or dual connectors 62 a and62 b are provided, system 100 a is configured to pump fluid to and froma dialyzer using a desired sequence of pump-to dialyzer strokes andpump-from dialyzer strokes. For example, a peristaltic pump operatingwith peristaltic pump portion 30 could operate in a pump-to direction tostroke balance chamber 50 ten times, each time delivering a known volumeof fluid out connector 62 a to the dialyzer. Afterward, the peristalticpump is reversed for a period of time causing for example twelve strokesof balance chamber 50 to occur, each time pulling a known amount offluid from the dialyzer through connector 62 b, through cassette 10 a,to one of the drain bags. The additional number of stokes pulling fluidfrom the dialyzer constitutes an amount of ultrafiltrate removed fromthe patient. Alternatively balance chamber 50 is driven magnetically asdescribed below in connection with FIGS. 26A and 26B.

It should be appreciated that system 100 a could also be used to performhemofiltration. Here, to-patient connector 62 a is connected to theextracorporeal circuit directly, such that injectable qualityreplacement fluid can be introduced upstream or downstream (or both) ofthe hemofilter. The port of the hemofilter is connected to from-patientport 62 b in a dual port configuration or to single port 62 a, whereinthe sequential stroke manner just described is used in either case. In asimilar matter, hemodiafiltration could be performed, wherein the lineconnected to to-patient connector 62 a is connected to both theextracorporeal circuit directly and an inlet of the dialyzer. Again, theoutlet of the dialyzer in HDF can be connected to from-patient port 62 bor the single port 62 a depending on the configuration of cassette 10 aused.

Referring now to FIG. 2, an alternative system 100 b employs analternative flexible sheeting cassette 10 b. System 100 b includes manyof the same components that system 100 a includes. For example, system100 b includes supply containers 12 a to 12 c and drain container 14. Asbefore, supply containers 12 a to 12 c are connected fluidly to cassette10 b via supply connectors 16 a to 16 c via supply lines 18 a to 18 c,respectively. Also, drain bag 14 is connected fluidly to drain connector22 via drainline 24. Connectors 16 a to 16 c and 22 are each connectedto flow paths 26 a to 26 d, wherein each of the flow paths has a valvecontact portion 28 a to 28 d, respectively. Flow paths 26 a to 26 d allfeed into a pump inlet manifold pathway 64 a.

One primary difference between system 100 b and system 100 a is thatsystem 100 b uses volumetric or membrane pumps rather than peristalticpumps. Here, an inlet manifold pathway 64 a communicates fluidly withpump inlet pathways 66 a and 66 b, which each lead fluidly to arespective volumetric or membrane pumping portion 70 a and 70 b. Valveactuators operating with valve contact portions 28 p and 28 q enablefluid to be pumped selectively through either volumetric pump portion 70a or 70 b as desired. Volumetric pump portions 70 a and 70 b operatewith a pneumatic and/or mechanical pump actuator located within thedialysis machine as described in more detail below in connection withFIGS. 9A to 9C. Alternatively, the volumetric pump portions are actuatedmagnetically as shown below in connection with FIG. 28.

In FIG. 2, pump outlet pathways 68 a and 68 b extend from the outletside of pump portions 70 a and 70 b, respectively, and feed into a pumpoutlet manifold pathway 64 b. Fluid leaves the pump outlet manifoldpathway 64 b then enters an alternative integral inline fluid heatingpathway 42 b Inline, integral fluid heating pathway 42 b is shown inmore detail operating with a fluid heater in connection with FIG. 10A.Any air that escapes from the dialysate or other medical fluid(including blood) during heating within fluid heating pathway 42 b canbe selectively removed from the system via inline vent 44. Oneembodiment for vent 44 is shown in detail below in connection with FIG.11. Air is alternatively pumped to drain or left in fluid heatingpathway 42 b. Cassette 10 b can be mounted in machine vertically withvent 44 pointing upwardly to allow air to escape cassette 10 bautomatically and without valve actuator and valve seat 28 h for suchactuator. Further vent 44 can be pointed upwardly when cassette 10 b isloaded such that valve actuator and valve seat 28 h can be eliminatedeven if cassette 10 b is loaded horizontally.

If no air is detected, heated dialysate is allowed via valve actuatorsoperating with contact portions 28 i and 28 h to be pumped to thepatient (dialyzer or hemofilter, etc.) via to-patient connector 62 a. Asdescribed above in connection with system 100 a, system 100 b canalternatively include a from-patient connector 62 b (not illustratedhere). In either configuration, system 100 b can perform sequential HD(including HHD), HF or HDF as described above.

In the illustrated configuration of system 100, flexible sheetingcassette 10 b is configured to perform PD, such as CAPD, tidal flow PDand APD. Here, as described above, after dialysate has been allowed todwell within the patient's peritoneum for a prescribed period of time,to-patient connector 62 a becomes a from-patient connector, whichreceives spent dialysate from the patient. In the illustratedembodiment, spent fluid is pulled back through fluid heating pathway 42b via pumps 70 a and 70 b, which push the spent dialysate to a suitabledrain bag or drain. In an alternative embodiment (not illustrated),cassette 10 b provides a suitable bypass pathway and corresponding valvecontact portions to enable returning spent fluid to bypass fluid heatingpathway 42 b.

As shown, one primary difference between system 100 b and system 100 ais the incorporation of fluid heating pathway 42 b into the flexiblesheeting cassette 10 b. Here, the corresponding heater is placed in thesame machine housing as the pump actuator and valve actuators. Asdiscussed above, the separate inline heater bag 40 of system 100 a canoperate alternatively with a heater housed in the same unit as the pumpand valve actuators of system 100 a or with a heater provided separatelyfrom the pump and valve actuator unit. It should be appreciated that theintegrated, inline pathway 42 b of system 100 b can be used with theperistaltic pump portion 30 and/or balance chamber 50 of system 100 a ofFIG. 1. Further, the separate heater bag 40 of system 100 a canalternatively be used with the volumetric pump portions 70 a and 70 b ofFIG. 2.

As discussed, one primary difference between system 100 b and system 100a is the use of volumetric or membrane pump portions 70 a and 70 b asopposed to the peristaltic type pump used above for system 100 a.Volumetric pump actuators operating with portions 70 a and 70 b pump aknown amount or volume of dialysate with each pump stroke. The totalvolume pumped by volumetric or membrane pump portions 70 a and 70 b isdetermined by counting the number of pump strokes. The advantage here isthat a separate volumetric control apparatus, such as balance chamber50, is not needed. Two pump actuators operate out of phase with portions70 a and 70 b to produce an at least substantially continuous flow ofdialysate to and from the patient.

All the materials described above for system 100 a are also applicableto like components of system 100 b. In operation, one of the supplyvalves 28 a to 28 c is opened to enable fresh dialysate to flow from oneof the supply bags 12 a to 12 c into one of pump portions 70 a and 70 b,via a respective supply pathway 26 a, 26 b or 26 c. Pumped fluid flowsthrough manifold 64 a, through inlet pathway 66 a or 66 b into pumpportion 70 a or 70 b, respectively. The fluid then flows throughrespective outlet pathway 68 a or 68 b, through outlet manifold 64 b,through heating path 42 b where it is heated, through to-patient fluidconnector 62 a into the patient.

Volumetric pump portions 70 a and 70 b can pump fluid to or from thepatient using different valve sequencing. For example, to pump fluid tothe patient the pump through portion 70 a and to pull fluid into pumpportion 70 a the valve actuator operable with valve contact portion 28 pis opened, while the valve actuator operable with valve contact portion28 r is closed. Next, the valves are switched to pump the volume out ofportion 70 a, through heating pathway 42 b to the patient. To run inreverse, e.g., drain the patient, the above-described valve states arereversed to pull spent fluid into pump portion 70 a and then to pump thespent fluid from pump portion 70 a to a suitable drain.

Referring now to FIG. 3, a system 100 c employing a third flexiblesheeting cassette 10 c is illustrated. System 100 c is similar to system100 a of FIG. 1 and includes many of the same components, such as supplybags 12 a to 12 c, drain bag 14, supply connectors 16 a to 16 c, drainconnector 22, and lines 18 a to 18 c connecting the supply bags toinlets connectors 16 a to 16 c, respectively. System 100 c also includesa line 24 leading from drain connector 22 to drain bag 14. Flexiblesheeting cassette 10 c includes the same valve contact portions 28 a to28 h as discussed above for system 100 a. System 100 c operates with aseparate heater bag 40 having a fluid heating pathway 42 a coupled toheater lines 38 a and 38 b and connectors 36 a and 36 b. The operationof vent 44 is as described above. Air is alternatively pumped to drainbag 14 or left in heater bag 40.

One primary difference between system 100 c and system 100 a is that ituses two separate peristaltic pump actuators operable with separateperistaltic pumping portions 30 a and 30 b. The illustratedconfiguration for the pumping portions is upstream of the fresh andspent inlets of the dual balance chambers 50 a and 50 b. Thisconfiguration allows for simultaneous, two-way pumping as discussedbelow.

System 100 c provides dual balance chambers 50 a and 50 b. As seen, eachbalance chamber 50 a and 50 e operates with balance chamber inletpathways 56 a and 56 b and balance chamber outlet pathways 58 a and 58b. Each of those pathways includes a respective valve contact portion 28j, 28 k, 28 l or 28 m, respectively.

Simultaneous, two-way pumping requires a to-patient pathway 60 aconnected fluidly to a to-patient connector 62 a and a from-patientpathway 60 b connected fluidly to a from-patient connector 62 b.From-patient pathway 60 b is connected fluidly to spent pump portion 30b and to balance chamber inlet pathways 56 a leading to balance chambers50 a and 50 b. Thus balance chamber inlet pathways 56 a are spent fluidinlets and the spent fluid is driven by a pump actuator operating withperistaltic pump portion 30 b.

Fluid inlet pathways 56 b on the other hand are connected fluidly topump outlet pathway 32 leading from supply pump portion 30 a. Thusbalance chamber inlet pathways 56 b are fresh fluid inlets receivingfresh fluid driven by a pump actuator operating with peristaltic pumpportion 30 a. As shown below however, balance chambers 50 a and 50 boperate as secondary pumps, which accept a volume of fresh or spentfluid from fresh supply pumping portion 30 a or from spent supplypumping portion 30 b, respectively, and expel a like amount of spent orfresh fluid, respectively.

On the outlet side of balance chambers 50 a and 50 b, to-patient pathway60 a is connected fluidly to outlet pathways 58 b. This overall pathallows fresh fluid to be delivered from the balance chambers 50(referring collectively to balance chambers 50 a and 50 b) to adialyzer, extracorporeal circuit or the patient's peritoneum dependingupon the therapy being used. Outlet pathways 58 a are connected fluidlyto a drain pathway 26 d, which is fed to drain bag 14 or one of supplybags 12 acting as a drain bag, as determined by drain valve contactportions 28 d, 28 u, 28 v and 28 w. Alternatively, drain 14 is sized tohold the volumes from each of the supply bags 12 a to 12 c, eliminatingcontact portions 28 u to 28 w and simplifying drain pathway 26 d.

In operation, system 100 c can simultaneously deliver and remove fluidto and from the patient. To do so, in one half-cycle, for example, valveactuators operating with seats 28 k and 28 l of balance chamber 50 a andvalve seats 28 j and 28 m of balance chamber 50 b are in an open-valvestate, while valve actuators operating with valve seats 28 and 28 m ofbalance chamber 50 a and valve seats 28 k and 28 l of balance chamber 50b are in a closed-valve state. This configuration allows pump portion 30a to deliver a volume of fresh solution through inlet pathway 56 b intobalance chamber 50 a, which in-turn forces a previously delivered likevolume of spent solution to leave balance chamber 50 a, through outletpathway 58 a, drain pathway 26 d, to drain 14 or one of the supply bags12 a or 12 b acting as a drain bag. Simultaneously, pump portion 30 bdelivers a volume of spent solution through inlet pathway 56 a intobalance chamber 50 b, which in turn forces a previously delivered likevolume of fresh solution to leave balance chambers 50 b, through outlet58 b and to-patient line 60 a to the patient.

Then, in a second half-cycle, valve seats 28 k and 28 l of balancechamber 50 a and valve seats 28 j and 28 m of balance chamber 50 b areclosed, while valve seats 28 j and 28 m of balance chamber 50 a andvalve seats 28 k and 28 l of balance chamber 50 b are opened. Thisconfiguration allows pump portion 30 a to deliver a volume of freshsolution through inlet pathway 56 b into balance chamber 50 b, which inturn forces a previously delivered like volume of spent solution toleave balance chamber 50 b, through outlet pathway 58 a and drainpathway 26 d, to drain or one of the supply bags 12 a or 12 b.Simultaneously, pump portion 30 b delivers a volume of spent solutionthrough from-patient line 60 b and inlet pathway 58 a into balancechamber 50 a, which in turn forces a previously delivered like volume offresh dialysate from balance chamber 50 a through outlet pathway 58 b,to-patient line 60 a and to the patient.

As shown and described, balance chambers 50 a and 50 b ensure that alike volume of fresh and spent dialysate is delivered to and removedfrom the patient in each half-cycle. System 100 c can remove excessfluid or ultrafiltrate in a number of ways. In one embodiment, bothbalance chambers 50 a and 50 b are filled with spent fluid. Next, valvecontact portions 28 l, 28 k and 28 n are opened and the pump actuatoroperating with pump portion 30 a is run in reverse, pulling fluid fromthe patient through to-patient line 62 a in the reverse direction. Thisaction causes spent fluid to be pushed out drain pathway 26 d to a drainvia the spent fluid pulled in via pumping portion 30 a. Now, both freshcompartments of balance chambers 50 are full of spent fluid and pumpportion 30 b causes spent fluid again to fill both spent compartments ofchambers 50 a and 50 b with spent fluid. This causes a delivery of spentfluid from both fresh compartments of chambers 50 to the patient. A netfluid loss occurs because this volume came from the patient instead ofthe source. Alternatively, a valved bypass line is provided (notillustrated) leading from the to-patient line 60 a to drain pathway 26d, so that the spent fluid is sent alternatively to a drain. The valvedbypass line increases the UF efficiency but adds extra valves and flowpaths. Either way, the above-described valve sequence is repeated asneeded to remove a necessary amount of ultrafiltrate.

The above-described UF embodiments are administered intermittently. Thatis, they occur in some sequence with the non-UF or balanced strokes. Forexample, the control unit operating the pump and valve actuators couldsequence system 100 c to administer twelve balanced strokes and thenthree UF strokes. By the end of therapy, the cumulative volume of the UFstrokes achieves the target UF volume, which is the volume of fluid thatneeds to be removed to return the patient to his or her “dry weight” asthat term is known in the art.

In an alternative embodiment, system 100 c provides a third peristalticpump operating with a third UF peristaltic pumping portion (notillustrated but configured and valved at least substantially the same aspumping portions 30 a and 30 b) and a third UF balance chamber (notillustrated but configured and valved at least substantially the same asbalance chambers 50 a and 50 b). In one embodiment, the inlet of the UFpumping portion tees into from-patient line 60 b or connects separatelyto a from-patient tube extending from to the patient to from-patientconnector 62 b.

The outlet of the UF pump portion feeds into both compartments of the UFbalance chamber. Valves are provided to allow the UF pump portion tofill a first compartment of the UF balance chamber with spent fluid,thus emptying the second compartment of the UF balance chamber of spentfluid. Next, the second compartment is filled, emptying the firstcompartment of spent fluid to complete a full cycle. In each cycle aknown amount of spent fluid is removed as UF. Fluid emptied from the UFbalance chamber is sent via drain pathway 26 d to drain 14 or one of thesupply bags 12 acting as a drain bag as described above.

The UF cycle is repeated as necessary to achieve the target UF removalvolume. Importantly, this can be done while pumping portions 30 a and 30b and balance chambers 50 a and 50 b deliver/remove a matched volume offresh/spent fluid to/from the patient. It may be beneficial to have theability to run the UF pumping portion and the UF balance chambercontinuously, e.g., at a constant rate or at a varying rate according toa patient profile over the course of therapy. To do so, the valvescontrolling the UF balance chamber are switched at greater or lesserfrequencies. The UF balance chamber may be sized differently, e.g.,smaller than balance chambers 50 a and 50 b for finer control of UF.

The third pump operating with the UF pumping portion can be run at anydesired speed relative to the pumps operating with balanced pumpingportions 30 a and 30 b. FIGS. 12A and 12B show peristaltic pumpembodiments in which a single roller drives two flexible sheetingcassette pumping portions. Given the above need for varying UF pumpspeed, the two pumping portions driven by the same roller (and thus atthe same speed) would be matched flow portions 30 a and 30 b in oneembodiment. The UF pumping portion would then operate with its ownroller.

In a further alternative embodiment, the third UF balance chamber isprovided but a third pumping portion is not. Here, the spent fluidpumping portion 30 b drives the UF balance chamber off of the returnpathway 60 b (downstream of spent fluid pumping portion 30 b) inaddition to balance chambers 50 a and 50 c. That is, the first andsecond compartments of the UF balance chamber are connected fluidly withthe return pathway 60 b downstream of spent fluid pumping portion 30 b.The valves controlling the UF balance chamber are again switched atgreater or lesser frequencies to control UF rate.

It should be appreciated that separate UF pumping portions andvolumetric control devices can also be provided for systems 100 a and100 b of FIGS. 1 and 2. For example, a separate peristaltic pumpingportion and balance chamber can be provided for system 100 a of FIG. 1.A third volumetric UF pump can be provided for system 100 b of FIG. 2.Such configurations allow for simultaneous balanced and UF strokes. Inany of the above-described configurations, any of the balancing chambersand/or UF pumping portion can be driven alternatively magnetically asshown below in connection with FIGS. 26A, 26B, and 27.

Referring now to FIG. 4, Detail IV of FIG. 1 is shown in detail and inperspective view. FIG. 4 shows one embodiment for sealing connectors,such as supply connectors 16 a to 16 c and drain connector 22 betweentwo plies or sheets 74 a and 74 b (which may be separate sheets orfolded from the same piece of material) of flexible sheeting cassette 10a. It should be appreciated however that the teachings of FIG. 4 applyto any of the sheeting cassettes 10 (referring collectively to flexiblesheeting cassettes 10 a, 10 b, 10 c, etc.) and also to any type ofconnector, such as to- and from-heater connectors 36 a and 36 b and to-and from-patient connectors 62 a and 62 b.

In the illustrated embodiment, connectors 16 (referring to 16 a to 16 ccollectively) and 22 each include a connector body 80, which can besemi-rigid or rigid. Suitable materials for body 80 include semi-rigidor rigid polymers or plastics, such as, Acrylic and Cyclic OlefinCopolymer (“COC”). Body 80 includes or defines a sealing apparatus 82,such as a luer fitting, ferreled fitting, other type of press-fit orthreaded seal. In one embodiment, supply lines 18 and drainline 24 (notshown) are removeably or permanently sealed around fitting 82. The sealcan rely on press-fit alone or be aided by a medically suitableadhesive, chemical bond or weld, such as an ultra-sonic, heat or othertype of weld.

In one alternative embodiment, lines 18 (referring to 18 a and 18 c ofFIG. 1 collectively) and 24 fit sealingly and removeably or permanentlyto body 80. A permanent seal can include any of the bonding techniquesdiscussed above, such as adhesive, heat energy, etc. In anotheralternative embodiment (not illustrated) one or both of first and secondplies 74 a and 74 b is thermo-formed to form a male port that extendsoutwardly from the front edge 78 a. Supply or drain lines 18 and 24 canthen seal removeably or permanently around or inside the thermoformedport via any of the techniques discussed above.

As illustrated by the rows of X's (used throughout the application toillustrate a sealed seam), first ply 74 a is sealed longitudinally atseals 72 a and 72 b to second ply 74 b on either side of body 80. Seals72 a and 72 b can also include a seal of plies 74 a and 74 b to body 80.As seen, seals 72 a and 72 b extend inwardly from bodies 80 to seal andform supply flow pathways 26 a to 26 c and drain pathway 26 d.

In the illustrated embodiment, pathways 26 are formed by thermo-forminga longitudinal, at least substantially semi-circular arc in one or bothfirst and second plies or sheets 74 a and 74 b. Suitable processes formaking such longitudinal arc include thermoforming and injectionmolding. In an alternative embodiment, the arc is not pre-formed,rather, seals 72 a and 72 b define relatively flat flow paths 26(referring collectively to flow paths 26 a to 26 d, etc.) and the pumpsare sized and configured to force fluid through the at leastsubstantially flat plies 74 a and 74 b forming pathways 26. Furtheralternatively, one or more temporary tube rod or other templateinstrument can be laid on sheet 74 a or 74 b. Sheet 74 a or 74 b isstretched over the tube or template and welded to sheet 74 b or 74 a,respectively. The tube or template is removed leaving pathways 26.

A seal 72 c is made along front edge 78 a of flexible sheeting cassette10 a. Seal 72 c includes a sheet 74 a to sheet 74 b seal in certainplaces and a circumferential sheet 74 a/74 b to body 80 seal atconnectors 16 and 22. A seal 72 d is made along side edge 78 b offlexible sheeting cassette 10 b. Seal 72 (referring collectively toseals 72 a, 72 b, 72 c, 72 d, etc.) can be made via any one or more ofthe adhesive, chemical or welding embodiments discussed herein. Further,edges 78 b can be formed alternatively by folding a single piece ofmaterial at edge 78 b to form first and second sheets 74 a and 74 b.Still further, edges 78 a and 78 b can be welded to a rigid frame thatprovides structural support for sheeting cassettes 10 a, 10 b and 10 c.The frame aids in the handling and loading of the cassette.

In the illustrated embodiment, bodies 80 of connectors 16 and 22 are atleast substantially cylindrical. In an alternative embodiment, bodies 80are flared or tapered to provide enhanced sealing surfaces for sealingto upper and lower plies 74 a and 74 b. One configuration for taperedbodies 80 is shown and described in U.S. patent application Ser. No.10/155,384, entitled Disposable Medical Fluid Unit Having Rigid Frame,filed May 24, 2002, owned by the assignee of the present application,the entire contents of which are incorporated herein by reference.

Valve contact portions or seals 28 a to 28 d in the illustratedembodiment are flat sections or indents formed or made at theappropriate positions along flow paths 26. The flat sections or indentscan be formed in the process of forming paths 26 or be made in paths 26after the paths are formed. The flats or indents tend to increase thecontact area with flat headed valve actuators. It is contemplatedhowever that valve contact portions or seals 28 do not have a differentconfiguration from the rest of flow paths 26 and are simply areas atwhich the valve actuator contacts the flow paths 26. Here, the headconfiguration and force of the valve actuator is sufficient to close thesemi-circular or circular flow paths 26 when called upon to do so. Thevalve actuator can be pneumatically, mechanically, hydraulically and/orelectrically actuated. For example, a fail-safe valve actuator is usedin one embodiment, which is closed via a spring force and opened via avacuum. The valve actuators are opened and closed pneumaticallyalternatively. Further, the valve actuators can be cams driven by a camshaft.

Referring now to FIG. 5, Detail V of FIG. 1 is shown in more detail andin perspective view. FIG. 5 shows one embodiment for peristaltic pumpportion 30 (including pump portions 30 a, 30 b, etc.). Pump portion 30includes an at least substantially circular flow path 84, which isformed using upper and lower plies 74 a and 74 b via any of the methodsdiscussed herein and includes any of the configurations discussed abovefor fluid pathways 26. Peristaltic pump inlet 86 and peristaltic pumpoutlet 88 communicate fluidly with peristaltic flow path 84 and withsupply pathways 26 a to 26 c and pump output pathway 32, respectively,shown above in connection with FIGS. 1 and 3. Inlet 86 and outlet 88 areplaced in an at least substantially parallel, adjacent relationship withrespect to each other in the illustrated embodiment to maximize thedistance or throw of peristaltic pumping pathway 84.

As shown, peristaltic pump portion 30 operates with a peristaltic pumpactuator 90. Peristaltic pump actuator 90 generally includes componentsknown to those of skill in the art, such as a drive shaft 92 and atleast one roller 94 driven rotatably by drive shaft 92. One differencebetween the peristaltic configuration of FIG. 5 and that of knownperistaltic pumps is that known pumps typically use round tubing that islooped inside of a circular race. That is, the outer circumference ofthe loop is abutted against the race. The drive shaft rollers contactthe inner circumference of the loop and pinch the tube radially againstthe race. In FIG. 5, on the other hand, a race or press-plate 126 islocated behind second sheet 74 b. The race or press-plate 126 is part ofthe dialysis machine in one embodiment and, for example, can be part ofa door that is closed against flexible sheeting cassette 10 a or 10 cafter it has been loaded into the machine. Rollers 94 are located withinthe machine on the opposing side of cassette 10 a or 10 c.

Rollers 94 spin in substantially a same plane in which sheets 74 a and74 b reside and press pathway 84 in multiple places against plate 126 todrive fluid from inlet 86 to outlet 88. In particular, shaft 92 spinssuch that rollers 94 create negative and positive pressure gradients todrive fluid from inlet 86 to outlet 88. The thermo-formed flow paths areconfigured to withstand, e.g., not collapse or close, forces created bythe vacuum or negative peristaltic pressures. As seen via the arrowsFIG. 5, shaft 92 can be driven bi-directionally if needed as describedabove.

Referring now to FIG. 6, one embodiment for balance chamber 50(referring generally to balance chambers 50 a, 50 b, etc.) used inflexible sheeting cassettes 10 a and 10 c is illustrated. FIG. 6 showsDetail VI of FIG. 1 shown in perspective view. FIGS. 7 and 8 arecross-section views of FIG. 6 taken along lines VII-VII and VIII-VIII,respectively, shown in FIG. 6. As seen in FIGS. 6 to 8, balance chamber50 uses three plies or sheets 74 a to 74 c of flexible material. Variousembodiments for sealing three separate plies together are discussedherein. Three sheets 74 a to 74 c may be completely separate or foldedtwice from the same piece of material.

As seen in FIG. 6 and discussed above, balance chamber 50 includes asealed circle 52 formed by a first seal 78 e shown by the circular axisbetween first sheet 74 a and second sheet 74 b. The chamber formedwithin the circular seal 72 e between sheets 74 a and 74 b, which formthe upper balance chamber compartment 54 a as seen also in FIG. 7. Asecond seal 72 f is shown in phantom in FIG. 6 in which it residesbeneath sheet 74 a and is made about the same sealed circle 52 betweensecond sheet 74 b and third sheet 74 c, which form lower balance chambercompartment 54 b. In an embodiment, seals 72 e and 72 f are made at thesame time or as the same seal, so that a single sealing process, e.g., awelding or chemical bonding process, forms both seals 72 e and 72 fsimultaneously and associated comparatively. It is contemplated,however, to form one of seals 72 e and 72 f first and thereafter formthe second of the two seals 72 e and 72 f. Seals 72 e and 72 f can bemade via any of the methods described herein. Additional seals (notillustrated) are made along the edges of the three sheets 74 a to 74 cand elsewhere in cassette 10 a or 10 c as discussed herein.

In the illustrated embodiment seal 72 e extends to form balance chamberinlet 56 a and balance chamber outlet 58 a. Enough of balance chamberoutlet 58 a is seen such that valve contact portion or seat 28 l shownin FIG. 1 is also seen in FIGS. 6 and 7. Seal 72 f also extends to formbalance chamber inlet 56 b and balance chamber outlet 58 b. Enough ofbalance chamber outlet 58 b is illustrated so that valve seat 28 m isshown in hidden and in phantom in FIG. 6 and is also seen in FIG. 8. Asseen in FIG. 1, balance chamber outlet pathways 58 a and 58 b combineinto two patient pathway 60 a. FIGS. 6 and 8 illustrate one embodimentfor enabling fluid to travel between two flexible sheeting pairs orlevels. As seen, middle flexible sheet 74 b defines an aperture oropening 96, which is located directly above the distal end of balancechamber outlet 58 b and is inline with balance chamber outlet 58 a andthe subsequent to-patient pathway 60 a. In this configuration, fluidexiting lower balance chamber compartment 54 b travels through balancechamber outlet 58 b, upwardly through second sheet 74 b via aperture 96,into balance chamber outlet 58 b and to patient pathway 60 a, which arelocated and defined by flexible sheets 74 a and 74 b.

FIG. 8 illustrates a cross section of sealed plies 74 a to 74 c from afront view as cassette 10 a is sectioned through pathways 58 a and 58 bshown in FIG. 6. As seen, in FIG. 8 valve seat 28 m is located laterallyoffset from valve seat 28 l, so that cooperating valve actuators canopen and close pathways 58 a and 58 b independently. That is, a valveactuator can close either valve seat 28 l or 28 m without also closingeither of flow path 58 b or 58 a, respectively. FIG. 8 also showsaperture 96 in cross section, which is formed in sheet 74 b and whichenables fluid communication between paths 58 a and 58 b, so that flowfrom upper and lower compartments 54 a and 54 b can be combined into topatient pathway 60 a. FIG. 8 further shows that pathways 58 a and 58 bcan be raised via thermo-forming or other method to provide a gapbetween the inner surface of plies 74 a and 74 c and the outer surfacesof ply 74 b.

Referring now to FIG. 7, one apparatus and method for operating balancechamber 50 (referring generally to each of the balance chambersdescribed herein) is illustrated. Balance chamber 50 is shown inoperation with a portion of the dialysis machine 100 a and 100 c(operating with cassettes 10 a and 10 c, respectively). Dialysis machine100 a or 100 c includes or defines first and second chamber formingmembers 102 a and 102 b. For example, one of members of 102 a or 102 bis stationary and configured to accept a flexible sheeting cassette,such as cassette 10 a or 10 c. The other of chamber forming members 102a or 102 b is part of a door that is closed onto the opposing side offlexible sheeting cassette 10 a and 10 c after it has been loaded intodialysis machine 100 a or 100 c.

Chamber forming members 102 a and 102 b each define or include a port104 to which a tube (not illustrated) is releasably or permanentlysecured via any of the methods and embodiments discussed above inconnection with connectors 16 and 22 of FIG. 4. In an embodiment, aftercassette 10 a or 10 c is loaded into machine 100 a or 100 c, a negativepressure or vacuum is drawn on ports 104, pulling first and third pliesor sheets 74 a and 74 c against the inner at least substantiallyspherically shaped cavities defined by first and second members 102 aand 102 b. Although members 102 a and 102 b are shown defining at leastsubstantially spherical shapes, other suitable cross-sectional shapesmaybe used, such as substantially triangular or substantiallytrapezoidal shapes. Further, although not illustrated, members 102 a and102 b can define air channels that extend radially from ports 104 invarious directions to help spread the vacuum across a larger surface ofplies 74 a and 74 c. Such channels are shown and described in U.S. Pat.No. 6,814,547, entitled Medical Fluid Pump, assigned to the assignee ofthe present application. Once sheets 74 a and 74 c are pulled via vacuumagainst the inner surface of chamber forming members 102 a and 102 b,respectively, balance chamber 50 is ready for operation. In analternative embodiment, negative pressure is not applied against sheets74 a and 74 c and thus ports 104 are not needed. Here, the positivepressure of the dialysate or fluid is enough to spread, respectively,sheets 74 a and 74 c against members 102 a and 102 b, respectively, andto drive middle sheet 74 b between sheets 74 a and 74 c.

FIG. 7 illustrates a state of operation in which no fluid has beendelivered to balance chamber 50. Accordingly, middle or driving sheet 74b is not pushed towards either upper sheet 74 a or lower sheet 74 c.Section VII-VII taken through the detail of FIG. 6, for FIG. 7 includesvalve seat 23 l. As seen in FIG. 8, valve seat 28 m is not aligned withvalve seat 28 l with respect to the section plane along line VII-VII ofFIG. 6. Accordingly, valve seat 28 m is not seen in the sectioned viewof FIG. 7 because that view valve seat 28 m in that view resides infront of valve seat 28 l. Valve seat 28 l is shown operating with avalve actuator 106, which is part of machine 100 a or 100 c. Forsimplicity, valve actuator 106 is shown as an entirely pneumaticallyoperated valve actuator. Here, positive air pressure is applied to theport of actuator 106 to force a plunger 108 to compress valve seat 28 lagainst second sheet 74 b to close balance chamber outlet 58 a. Actuator106 includes an o-ring seal 110, which creates a sliding seal betweenplunger 108 in the inner, e.g., cylindrical housing of valve actuator106. To open balance chamber outlet 58 a, a negative pressure is appliedto port 106, pulling plunger 108 upwards against stop 112, enablingfluid to open seat 28 l and flow outwardly from upper balance chambercompartment 54 a through balance chamber outlet 58 a. FIGS. 6 to 8 donot show valve seats 28 j, 28 k or 28 l which communicate with valveactuators, such as valve actuator 106. These actuators and seats controlthe inlet of balance chamber 50 a and the inlet and outlet of balancechamber 50 b of FIG. 1.

In operation, to fill upper balance chamber compartment 54 a, plunger108 is pressurized and closes valve seat 28 l and balance chamber outlet58 a. The valve actuator 106 operating with balance chamber inlet 56 ais opened, enabling fluid to fill upper balance chamber compartment 54a. If fluid has already filled lower compartment 54 b, the fluidentering compartment 54 a pushes the fluid from lower balance chambercompartment 54 b, through balance chamber outlet 58 b to itsdestination. To do so, a valve actuator 106 operating with balancechamber outlet 58 b is opened, while a valve actuator 106 operating withinlet 56 b is closed. Because the volume defined by compartments 54 aand 54 b is fixed and because second sheet 74 b is pushed all the wayagainst sheets 74 a or 74 c in each half stroke, the same volume offluid is outputted through balance chamber outlets 58 a and 58 b in eachhalf stroke. Accordingly, flexible sheets 74 a and 74 c are made of asuitably stretchable, compliant and leak-free material such as one ofthose materials listed above for sheets 74 (referring collectively tosheets 74 a to 74 c). As discussed below in connection with FIGS. 26Aand 26B, sheet 74 b is made alternatively to be magnetic and drivenalternatively magnetically.

Referring now to FIGS. 9A to 9C one apparatus and method of operatingvolumetric pumps 70 is illustrated. The portion of cassette 10 b shownin FIG. 2 and marked as Detail IX is shown in front, cross-sectionedview in FIGS. 9A to 9C., which shows volumetric pump 70 b. The teachingswith respect to 70 b are applicable to volumetric pump 70 a.

Volumetric pump 70 b is shown operating with a dialysis machine 100 b,which uses cassette 10 b. Machine 100 b includes first and second pumpchamber forming members 114 a and 114 b, which define the shape of thevolumetric pump 70 b. Cassette 10 b is configured to be loaded withinthe machine 100 b such that a circular flexible membrane portion ofcassette 10 b as seen in FIG. 2 is in alignment with the sphericallyshaped chamber defined by pump chamber forming members 114 a and 114 b.Also, valve seats 28 q and 28 s are aligned with valve actuators 106shown in FIGS. 9A to 9C. Valve actuators 106 operate as described abovein connection with FIG. 7 and include a plunger 108, which slides backand forth within the actuator body.

Chamber 70 b uses first and second flexible sheets 74 a and 74 b. Firstand second pump chamber forming members 114 a and 114 b each include aport 104 described above in connection with FIG. 7. As discussed below,negative and positive pressure are used to drain sheets 74 a and 74 b.Alternatively, one of sheets 74 a or 74 b can be driven mechanically. Asuitable hybrid mechanical/pneumatic pump is shown and described in U.S.Pat. No. 6,819,547 listed above. Although the spherical shape shown inFIGS. 9 a to 9 c is one suitable shape, other shapes could be definedfor volumetric pump 70, such as a trapezoidal or triangular shape.

FIG. 9A shows an initial state for volumetric pump 70 b. Here, negativepressure is applied to port 104 of chamber forming member 114 b, whichpulls second flexible sheet 74 b to conform with the inner surface ofsecond chamber forming member 114 b. At the same time, positive pressureis applied to port 104 of first pump chamber forming member 114 a. Thepositive pressure causes first flexible sheet 74 a to be pressed againstsecond flexible sheet 74 b. In FIG. 9A, a positive pressure is appliedto both valve actuators 106, closing valve seats 28 q and 28 s. Again,valve actuators 106 can be any combination of pneumatic, mechanicaland/or electrically operated. As further seen in FIG. 9A, dialysate ormedical fluid (including blood) 116 is pressurized against valve seat 28q, but is precluded from entering into the sealed chamber of volumetricpump 70 b.

In FIG. 9B, the negative pressure at port 104 of lower pump chamberforming member 114 b is maintained as is the positive pressure appliedto valve actuator 106 at valve seat 28 s. A negative pressure is appliedto valve actuator 106 at valve seat 28 q, which pulls and holds plunger108 to and against stop 112, allowing fluid 116 to flow through pumpinlet pathway 66 b and into the chamber of volumetric pump 70 b. Theforce of fluid 116, e.g., via gravity may be enough to cause firstflexible member 74 a to be pushed against inner surface of upper pumpchamber forming member 114 a. Alternatively, a negative pressure can beapplied at port 104 of member 114 a to pull first flexible sheet 74 aagainst the inner surface of the member. This action causes a vacuum,which pulls fluid 116 into the pump chamber. As with the peristalticpump, the thermo-formed flow paths are configured to withstand, e.g.,not collapse, under the negative pressure of the membrane pumping. Ineither case, fluid 116 fills the at least substantially spherical cavitybetween sheets 74 a and 74 b and stops against valve seat 28 s, which isstill in its closed position.

In FIG. 9C, valve seat 28 q is closed, while valve seat 28 s is opened.Negative pressure is maintained at lower port 104, so that sheet 74 b ispulled against member 114 b. Here, a positive pressure is applied toport 104, closing first flexible sheet 74 a against second flexiblesheet 74 b, causing fluid 116 to be pushed out of the at leastsubstantially spherical chamber of volumetric pump 70 b, through pumpoutlet pathway 68 b, to its desired destination. First and secondmembranes 74 a and 74 b are now at the position showed in FIG. 9A, sothat pump 70 b is able to repeat the above described cycle as soon asvalve seat 28 s is closed. As shown below in connection with FIG. 28,membranes 74 a and 74 b are made alternatively to be magnetic and drivenalternatively magnetically.

The pump out and fill strokes of pumps 70 a and 70 b in FIG. 2 can bestaggered such that the flow of dialysate or medical fluid (includingblood) through cassette 10 b is at least substantially continuous.Because the volume formed by the chamber of members 114 a and 114 b isknown and because first flexible sheet 74 a is moved repeatedly to theupper and lower surfaces of the chambers, the volume of fluid pumpedwith each stroke is known and repeatable. Accordingly, a separatevolumetric control apparatus, such as balance chamber 50, is not needed.The total volume of fluid pumped is equal to the volume of each strokemultiplied by the number of strokes. UF is controlled via one of themethods discussed above.

The volumetrically controlled chambers of balance chamber 50 andvolumetric pumps 70 are formed in an embodiment via the respectivecircular seals. In an alternative embodiment, the respective seals aremade larger in diameter than needed to achieve the desired volume. Here,a seal between the sheets 74 is created by the pressure of the doorpressing against the machine, or a first machine part pressing against asecond machine. As shown and discussed in connection with FIGS. 24A and24B, the machine seal is sized to form the proper diameter sphere toachieve the desired volume. The mechanical clamping seal lessensalignment constraints. The machine to machine seal can be securedmanually, e.g., via a lever or lock, clamps, cam-action press-fit, etc.or secured additionally or alternatively formed with the help ofpneumatic or electromechanical pressure. FIGS. 25A and 25B discussedbelow show embodiments for fluid heating pathways formed via mechanicalclamping and a heater operable with such fluid heating pathway. FIGS.26A, 26B and 28 discussed below show embodiments of balance chamber andvolumetric pump portions of the flexible sheeting cassette,respectively, formed via mechanical clamping and one embodiment fordriving the membranes within the balance and pump chambers.

Referring now to FIGS. 10A and 10B, two different embodiments for anintegrated heater path for the flexible sheeting cassettes discussedherein are illustrated. FIG. 10A illustrates Detail X of flexiblesheeting cassette 10 b shown in FIG. 2. FIG. 10B shows an alternativethree-layer, dual-sided heater path portion. FIG. 10A shows heater orheater plates 118, while FIG. 10B shows dual heaters or heater plates118 a and 118 b. Heaters or heater plates 118 (referring collectively toheater 118 of FIG. 10A and heater plates 118 a and 118 b of FIG. 10B)can perform any suitable mode of heat transfer, such as electricresistance, inductive, radiant, convective and any combination thereof.As shown in FIG. 10A, heater 118 is continuous beneath fluid heatingpathway 42 b. In FIG. 10B, heater elements 118 a and 118 b are localizedaround the fluid pathways 42 c and 42 d of the flexible sheetingcassette.

In FIG. 10A, fluid heating pathway 42 b is made of first and secondsheets 74 a and 74 b. A semi-circular or other suitable cross-sectionalshaped serpentine pathway is formed in sheet 74 a via any of theapparatuses and methods discussed above in connection with FIG. 4.Alternatively, both sheets 74 a and 74 b can form semi-circular halves,which together form a circular whole. If so, heater 118 can be formed ortailored with a semi-circular indented heating pathway to increasesurface contact. A continuous outer seal 72 g is made around the outsideof the loops or serpentine twists of fluid heating pathway 42 b. Acontinuous inner seal 72 h is made along the inner curve of pathway 42b. Seals 72 g and 72 h are made via any of the methods discussed above.Edge seal 72 i is also made along edge 78 c as seen in FIG. 10A.Alternatively, edge 78 c is made via a fold. In operation, dialysate orfluid flows through pathway 42 b and is heated via heat energy fromheater 118.

In FIG. 10A, flexible sheeting cassette 10 b is loaded on top of or isabutted vertically against heater 118. In FIG. 10B, the flexiblesheeting cassette is loaded between two insulative housings 120 a and120 b. Heater elements 118 a are fixed within insulative heater housing120 a. Heater elements 118 b are likewise fixed in insulative heaterhousing 120 b. Housings 120 a and 120 b may be part of the dialysismachine or part of a separate heater.

The fluid heating pathways 42 b and 42 c of FIG. 10B are formed fromthree sheets 74 a, 74 b and 74 c. Second sheet 74 b serves as a backingto the thermally formed pathways 42 c and 42 d in sheets 74 a to 74 c.Sheets 74 a and 74 c are sealed at once or at different times to middlesheet 74 b via any of the sealing methods discussed above. As seenadditionally in FIG. 10B, apertures 96 are made in second sheet 74 b toenable dialysate to flow from the lower fluid heating pathway 42 d ofthird sheet 74 c into the upper fluid heating pathway 42 c of sheet 74 aor vice versa. FIG. 10B therefore provides an efficient fluid heatingapparatus, which in essence doubles the heating capacity for the samesurface area versus the flexible sheeting cassette shown in FIG. 10A.Dual pathways such as the pathway 42 d could also be made with aseparate heater bag 40 of FIGS. 1 and 3.

Referring now to FIG. 11, one embodiment for mounting vent 44 into oneof the flexible sheeting cassettes 10 (referring collectively toflexible sheeting cassettes 10 a to 10 c) is illustrated. In particular,FIG. 11 shows Detail XI of flexible sheeting cassettes 10 b of FIG. 11.Flexible sheeting cassette 10 b includes first and second flexiblesheets 74 a and 74 b. Those sheets are sealed around vent 44, whichincludes a vent body 46 and a filter 48. Filter 48 in one embodiment isa hydrophobic membrane or other type of filter that allows air but notfluid or dialysate to pass through such filter. Vent 44 is fixed tosheets 74 a and 74 b in much the same manner as connectors 16 and 22 ofFIG. 4. To that end, seals 72 a and 72 b are made on either side of body46 of filter 48 and/or to body 46 itself. Seals 72 a and 72 b extend toform a fluid pathway, which can be aided by a thermo-formed shapecreated or in one or both of sheets 74 a and 74 b.

In operation, if air is detected in heated dialysate, a valve seat 28 has shown in FIGS. 1 to 3 is opened, allowing the fluid to reach vent 44and push the air through vent 48. Afterwards, the fluid is pumped to itsdesired destination. Alternatively, as described above, vent 44 ispointed vertically when its associated cassette is mounted, so that aseparate valve actuator and seat are not needed.

Referring now to FIG. 12A, one embodiment for driving fluid through twoflow paths using a single peristaltic pump actuator 90 is illustrated.Actuator 90 includes a drive shaft 92 and rollers 94 described above inconnection with FIG. 5. Flexible sheeting cassette, e.g., two pumpcassette 10 c, when loaded, is slid horizontally or vertically over ashaft 122, such that a slot 124 in sheets 74 a and 74 b slides over ashaft 98 of peristaltic pump actuator 90. Rollers 94 drive fluid throughboth pumping portions 30 a and 30 b shown for example in cassette 10 cof FIG. 3. Cassette 10 c is mounted such that second sheet 74 b isabutted against race plates 126 a and 126 b, which provide a rigidsurface against which the flow paths of pumping portions 30 a and 30 bcan be compressed by rollers 94, similar to press-plate 126 of FIG. 5.In the illustrated embodiment, rollers 94 drive fluid in the samedirection into and out of pumping portions 30 a and 30 b. As discussedabove, one use for the configuration of FIG. 12 is to provide a singleperistaltic pump actuator 90 that drives two pumping portions 30 a and30 b, which in turn feed the inlets of balance chambers 50 a and 50 bwith fresh or spent fluid.

Referring now to FIG. 12B, a second embodiment for using a singleperistaltic pump actuator 90 to drive fluid through two pumping flowpaths is illustrated. Here, peristaltic pumping portions 30 a and 30 bare configured as semi-circles or half-circles. Shaft 92 spins rollers94 (actuator 90 can have any suitable number of rollers 94) through afull 260 degrees to drive fluid through both fluid pathways of pumpingportions 30 a and 30 b. A suitable race plate (not illustrated), such asrace plate 126 of FIG. 5, is mounted behind flexible sheeting cassette10 b to provide a rigid surface against which rollers 94 can compressthe raised pathways 84 a and 84 b of pumping portions 30 a and 30 b.Unlike the dual pumping embodiment of FIG. 12A, the dual pumpingembodiment of FIG. 12B drives fluid in opposite directions as seen byoppositely disposed inlets 86 a/86 b and outlets 88 a/88 b. In both theembodiments of FIGS. 12A and 12B, however, shaft 92 can spin in eitherof two directions as shown by the arrows in FIG. 12B.

Dialysis machine 100 (referring collectively to each of the machines 100a, 100 b, etc.) uses many different sensors, such as pressure sensors,flow sensors, temperature sensors, air bubble detectors, solutionidentification detectors to check for example for peritonitis,composition and pH, conductivity sensors and ultrasound sensors, e.g.,for air or blood detection. Those sensors are used typically to sensesome parameter of the dialysate or fluid being pumped through one of theflexible sheeting cassettes 10.

Referring now to FIG. 13, one embodiment for operating a sensor 130 withany one of the flexible sheeting cassettes 10 a to 10 c is illustrated.Sensor 130 can be any of the above-described types of sensors andincludes leads or wires 132 that lead to a control unit or controller ofdialysis machine 100. Sensor 130 senses a parameter of dialysate ormedical fluid (including blood) flowing through a flow path 128.Cassette 10 (any cassette herein) is mounted such that a sensing area134 is aligned with sensor 130. Sensing area 134 is an expanded flowpath area defined by seals 72 a and 72 b, which slows down the flow offluid, and can increase sensing time and accuracy. Seals 72 a and 72 bare made via any of the methods and embodiments discussed above. Sensingarea 134 is shaped and sized to conform to the head of sensor 130.

Referring now to FIG. 14, one embodiment for making different sealsbetween three sheets 74 of material is illustrated. In FIG. 14, sheets74 b and 74 c are illustrated. Sheet 74 a (not illustrated) is sealed tothe top of sheet 74 b. A flow path 128 is made between sheets 74 b and74 c. As illustrated, a thermo-formed indent or raised portion is madein sheet 74 c, which is then sealed to sheet 74 b via any of thedifferent methods discussed above for seals 72 a and 72 b. Next, aprintable adhesive is deposited on the upper surface of sheet 74 b alongseal lines 72 j and 72 k. One suitable printable adhesive iscyclohexanone, e.g., for polyvinyl chloride (“PVC”) sheeting, or apolyester elastomer for other types of sheeting. Next, sheet or ply 74 ais placed as desired onto the top of sheet 74 b. Radio frequency (“RF”),ultraviolet (“UV”) energy or heat is then applied to adhesive seal lines72 j and 72 k to activate the printed adhesive along the appliedpattern, sealing sheet 74 a to 74 b. In this manner, the three sheets 72a to 72 c can form any desired seal pattern (same or different) betweensheets 74 a and 74 b and between sheets 74 b and 74 c.

Referring now to FIG. 15, another method for selectively sealing threesheets 74 a to 74 c of flexible material to form a flexible sheetingcassette is illustrated. A sealed seam 136 extends along one length ofthe cassette 10 d, for example at or near the middle of the other lengthof the cassette. Seam 136 enables the cassette to be maneuvered andfolded to make selectable seams in the three different sheets 74 a to 74c. This method applies to any flexible sheeting cassettes discussedabove. For purposes of illustration, flexible sheeting cassette 10 d ofFIG. 15 includes the single peristaltic pump 30 and balance chamber 50of FIG. 1 with an incorporated fluid heating pathway 42 b of FIG. 2. Asshown above, many features of the flexible sheeting cassette requireonly two sheets 74 a and 74 b. Other components such as balance chamber50 require three sheets 74 a to 74 c. It is therefore contemplated toprovide a cassette 10 d, which includes three sheets or plies 74 inareas requiring three sheets and only two sheets 74 a and 74 b in otherareas of cassette 10 d requiring only two sheets. In cassette 10 d,three sheets 74 a to 74 c are used alternatively over the whole cassette10 d. Again, sheets 74 a to 74 c can be separate or formed by folding asingle piece of material one or more times.

The left side of cassette 10 d is used to make the three layer dualsided heating flow paths 42 c and 42 d discussed above in connectionwith FIG. 10B. As illustrated, one of the outwardly facing flow paths,such as flow path 42 d is formed first by sealing sheets 74 b and 74 ctogether. Next, sheet 74 a is sealed to the combination of sheets 74 band 74 c. In an embodiment, sheet 74 a is sealed to the combination ofsheets 74 b and 74 c via the printable adhesive described above. Inanother embodiment, enough energy is applied to the outside of sheet 74a and 74 c to chemically bond or melt sheets 74 a and 74 b together.Further alternatively, sheets 74 a to 74 c can be secured to form fluidheating pathways 42 c and 42 d simultaneously. Middle sheet 74 b definesapertures 96 as discussed above that reside between fluid heatingpathways 42 c and 42 d.

The right side of cassette 10 d is used to form balance chamber 50,peristaltic pump 30, pressure sensing area 134, fluid flow pathways 26 ato 26 d and other flow paths associated with the above-listedcomponents. Here, flexible sheets 74 a and 74 b are sealed togetherfirst, after which sheet 74 c is sealed to sheet 74 b, e.g., to completebalance chamber 50. Although not illustrated, additional flow paths canbe formed between sheets 74 b and 74 c, with one or more apertures 96allowing fluid to flow from flow paths or flow apparatuses formed viasheet 74 a and 74 b and ones formed between sheets 74 b and 74 c. Sheet74 c can be sealed to sheet 74 b via the printable adhesive oralternatively or additionally by applying energy through all threesheets 74 a to 74 c.

As illustrated, pump output pathway 32 extends from peristaltic pumpingportion 30 across seam 136, through mating apertures defined in sheets74 a and 74 b, into the lower fluid heating pathway 42 d, through itsserpentine path, back through another set of mating apertures in sheets74 a and 74 b, into and through upper fluid heating pathway 42 c, beforeextending into balance chamber 50 and out to patient connector 62 a.

Referring now to FIG. 16, another method for sealing three sheets 74 ato 74 c together is illustrated. In FIG. 16, layers 74 a to 74 c aresealed using die sealing apparatuses 136 a and 136 b using machinerybuilt for example by KIEFEL Extrusion GmbH, Cornelius-Heyl-Str.49, 67547Worms/Germany. Apparatuses 136 a and 136 b apply heat to sheets 74 a to74 c in a predefined die pattern. The die pattern includes areas inwhich all three sheets 74 a to 74 c are sealed together and other areasin which only two of sheets 74 a and 74 b or 74 b and 74 c are sealedtogether.

In a conductive die sealing machine, each die apparatus 136 a and 136 bis controlled to output a desired amount of heat in direct contact withouter sheets 74 a and 74 c. For example, die apparatus 136 a can be setto output more heat than die apparatus 136 b. Using this conductive typeof heating, if it is desired to seal middle layer 74 b only to sheet 74a or 74 c, apparatus 136 a or 136 b on the non-sealing side of eithersheet 74 a or sheet 74 b is set to deliver a lesser amount of heat toprevent sealing between that sheet and middle sheet 74 b. The heat ofthe opposing die apparatus 136 a or 136 b contacting the sheet 74 a or74 c that is to form a seal with sheet 74 b is set to output a higheramount of heat, enough to melt the two sheets and seal the sheets in adesired pattern. The temperatures of hot and cold die apparatuses 136 aand 136 b are set to create a temperature profile that is higher thanthe melting temperature of middle layer 136 b on the side to be sealedand lower on the opposing side of sheet 136 b to prevent this side ofthe middle layer from melting. To this end, it may be that one of dieapparatuses is de-energized completely. The die machine is accordinglycapable of controlling the heat outputs of each apparatus 136 a and 136b independently to heat the different sheets 74 a to 74 c to the desiredtemperatures.

In another embodiment, the die sealing machine is of a radio frequency(“RF”) type. Here, one of the apparatuses 136 a and 136 b is positiveand the other is negative and direct or indirect contact with sheets 74a and 74 c. RF-type sealing is especially well-suited for sealing PVC,e.g., PVC tubing and PVC sheeting, although it can be used to seal otherkinds of tubing and sheeting materials listed herein. RF-type sealingcan be used in the embodiment of FIG. 15, for example, to seal the threesheets in multiple steps.

Referring now to FIGS. 17, 18, 19A and 19B, in an alternativeembodiment, a cassette 10 e includes a flexible portion 138 and a rigidportion 140. Flexible portion 138 includes first sheet 74 a and secondsheet 74 b. Peristaltic pumping portion 30 and inline fluid heatingpathway 42 b are formed via sheets 74 a and 74 b in flexible portion 138in any manner described above. With cassette 10 e, however, balancechamber 50 is formed using two sheets 74 a and 74 b instead of the threesheet version described above. Here, balance chamber 50 is formedpartially via a rigid chamber 142 formed in rigid portion 140. As seenin FIG. 18, flexible portion 138 is folded under or otherwise attachedto the underside of rigid portion 140. When this occurs, the flexiblemembrane portion of balance chamber 50 aligns with and is thereaftersealed to rigid chamber 142 of rigid portion 140.

FIG. 18 also shows heater 118 operating with heating pathway 42 b andperistaltic pump actuator 90 operating with peristaltic pumping portion30. Valve actuators, such as actuators 106 discussed above, are providedin valve actuation unit 144. Valve actuation unit 144 resides on theopposing side of cassette 10 e from heater 118 and pump actuator 90. Inthe illustrated embodiment valve actuation unit 144 can be part of adoor that presses valve actuators 106, heater 118 and pump actuator 90in place against the appropriate positions of cassette 10 e.

Valve seats, such as seats 28 a to 28 d, are provided as part of rigidportion 140 of cassette 10 e. Rigid flow paths, such as flow paths 26 ato 26 d, 32, 58 a and 58 b, communicate with pumping portion 30, balancechamber 50, their associated flow paths and fluid heating pathway 42 bof flexible portion 138 via apertures, such as apertures 96 provided inone or more sheets 74 b and 74 a with the rigid fluid pathways.

Regarding balance chamber 50, flow paths 56 a and 58 a flow from theflexible portion of balance chamber 50 of flexible portion 138 to rigidpathways defined by rigid portion 140. Valve seats 28 j to 28 m arelocated in rigid portion 140. Further, pathways 56 b and 58 b leading torigid chamber 142 are also provided in rigid portion 140.

Referring now to FIGS. 19A and 19B, a balance chamber 50 constructedfrom rigid chamber 142 of rigid portion 140 and two flexible sheets 74 aand 74 b of flexible portion 138 of cassette 10 e is illustrated. Whilebalance chamber 50 of FIGS. 19A and 19B is shown in connection withcassette 10 e having rigid portion 140 and flexible portion 138, it isexpressly contemplated to provide the balance chamber 50 of FIGS. 19Aand 19B with a flexible sheeting cassette in which having a sole rigidportion 142. That is, rigid chamber 142 can be provided independently orseparately and is not required to part of a larger rigid portion 140.

As illustrated, sheet 74 a butts against a rigid backing member 146.Rigid backing member 146 can be provided with cassette 10 d or isalternatively part of dialysis machine 100 d operating with cassette 10d. Backing plate 146 constrains lower balance chamber compartment 54 bto expand into the cavity formed by rigid chamber 142 when lower balancechamber compartment 54 d is filled. Valve seats 28 k and 28 m are shownfiguratively in cooperation with rigid chamber 142. Likewise, valveseats 28 j and 28 l are shown figuratively in cooperation with sheets 74a and 74 b. For purposes of illustration, valve seats are shown with an“X” when in a closed fluid state and without an “X” when in an open orfluid flow state.

In FIG. 19A, the valve actuators operating with valve seats 28 j and 28m cause the seats to be closed, while the valve actuators operating withvalve seats 28 k and 28 l cause those seats to be open. In this valvestate configuration, upper balance chamber compartment 54 a fills with avolume of fluid 116, while lower balance chamber compartment 54 b expelsa like volume of fluid to a desired destination. In FIG. 19B, the valveactuators operating with valve seats 28 k and 28 l cause those seats tobe closed, while the actuators operating with valve seats 28 j and 28 mcause those seats to be open. Here, lower balance chamber compartment 54b fills with fluid 116, while a like volume of fluid is dispensed fromupper balance chamber compartment 54 a, past valve seat 28 m, to adesired destination.

The rigid chamber version of balance chamber 50 can be provided singlyin a cassette, for example as shown in FIGS. 1 and 17 with cassettes 28a and 28 d. Alternatively, two or more rigid chamber versions of balancechamber 50 are provided in a cassette, such as discussed in connectionwith cassette 10 c of FIG. 3. Under normal matched flow circumstances,fresh fluid enters one of the compartments 54 a or 54 b dispensing spentfluid from the other compartment, and vice versa. Rigid chamber balancechamber 50 can alternatively be used for UF only, in which case spentfluid is delivered to both compartments 54 a and 54 b.

Referring now to FIGS. 20A to 20D, an alternative embodiment for balancechamber 50 employing the flexible sheet 74 a to 74 c is illustrated.Balance chamber 50 in FIGS. 20A to 20D incorporates tubes 156 a and 156b as balance chamber inlet and tubes 158 a and 158 b as balance chamberoutlets. Tubes 156 a, 156 b, 158 a and 158 b can be made of any suitablemedical grade material, such as PVC, non-DEHP PVC, polybutadiene (“PB”),ethylene vinyl acetate (“EVA”), polypropylene (“PP”) blend, polyethylene(“PE”) blend, Kraton blend and polyolefin blends. The tubes are sealedin place along seals 72 l. Upper and lower seals 72 e and 72 f discussedabove in connection with FIGS. 6 and 7 are made to form upper balancechamber compartment 54 a and lower balance chamber compartment 54 b.Inlet tube 156 a and outlet tube 158 a communicate fluidly with upperbalance chamber compartment 54 a, while inlet tube 156 b and outlet tube158 b communicate fluidly with lower balance chamber compartment 54 b.

Inner ends 160 of balance chamber inlet tubes 156 a and 156 b andbalance chamber outlet tubes 158 a and 158 b are configured to bealigned with the circular chambers formed by seals 72 e and 72 f, so asto allow first and third sheets 74 a and 74 c to be pulled apart againstrespective inner walls of the balance chamber formerly members locatedinside the dialysis machine, such as chamber walls 102 a and 102 b shownin FIG. 7. Middle sheet 74 b is sealed to the bottom of tubes 156 a and158 a so that fluid entering from tube 156 a can flow only into uppercompartment 54 a. Middle sheet 74 b is sealed around the top of innerends 160 of tubes 156 b and 158 b, so that fluid entering sheet and tubetype balance chamber 50 through 156 b can enter only into bottomcompartment 54 b of balance chamber 50. Otherwise, middle sheet 74 b isfree to move back and forth within outer sheets 74 a and 74 c whenbalance chamber 50 is in operation.

FIGS. 20C and 20D illustrate that sheets 74 a to 74 c have semicircularbends 76. Bends 76 can be preformed or at least partially preformed,e.g., via thermoforming. Alternatively, bends 76 are formed during theprocess of sealing sheets 74 a to 74 c about tubes 156 and 158. Bends 76are made outwardly in outer sheets 74 a and 74 c. Bends 76 in middlesheet 74 b alternate direction as needed. Depending on which side isbeing welded, seal 72 l may weld two sheets 74 a/74 b or 74 b/74 c orone sheet 74 a or 74 b to tubes 156 a or 156 b.

In the illustrated embodiment, sheet and tube type balance chamber 50 isprovided as a separate apparatus that can be connected fluidly toanother part of the disposable unit or the dialysis system. To that end,tubes 156 a to 158 b can be as long as needed to be connected to theother part of the dialysate circuit. In an alternative embodiment, twoor more balance chambers 50 having the configuration of FIGS. 20A to 20Dare formed via sheets 74 a to 74 c and two or more sets of tubes 156 ato 158 b. Further alternatively, one or more of the balance chambers 50of FIGS. 20A to 20D is provided in a cassette such as cassettes 10 a to10 d, which contain most if not all of the components of the dialysatecircuit, notwithstanding the bags, patient connection and associatedtubing.

Tubes 156 a to 158 b can have or include valve seats, such as valveseats 28 j to 28 l described above in connection with the balancechamber 50 of FIG. 1. Alternatively, automated pinch or tubing clampsare used to clamp a portion of tubes 156 a to 158 b without needing amodified valve seat area. Balance chamber 50 of FIGS. 20A to 20D can beused in any of the cassettes described herein employing one or morebalance chamber.

Referring now to FIGS. 21A to 21G, an alternative flexible sheetingcassette 10 e is shown in operation with a hemodialysis machine 100 e,which in one preferred embodiment is a home hemodialysis (“HHD”)machine. Alternatively. cassette 10 e can be used with any of thedialysis therapies discussed herein. As discussed in the parentapplication, hemodialysis typically takes place in a clinic or center,in which the dialysate is made online using a water source andconcentrates. In a home setting, a similar type of online dialysategeneration unit is also used typically. These units are large andrequire the dialysis machine to be connected to a source of water. Inthe embodiment illustrated in FIGS. 21A to 21G and in the parentapplication, an alternative system is shown, which uses dialysatesupplied from one or more supply bag, and which can provide convectiveclearance in addition to diffusive clearance. Alternatively, the blooddisposable is combined with the dialysate disposable. In FIGS. 21B and21F, a separate blood cassette 150 is provided.

FIGS. 21A and 21C to 21E illustrate flexible sheeting cassette 10 e.Cassette 21 e differs from the above described cassettes in a number ofways. One difference is that separate peristaltic pumping tubes 148 and154 are used instead of the flexible sheeting cassette pumping portion30 shown and described above for example in connection with FIGS. 1, 3and 5. A second difference is that the manifolding of the differentsupply and drain bags is done via tubing external to the flexible sheets74 a to 74 c of cassette 10 e. In FIG. 21A, the peristaltic pumpactuators operating with dialysate line 148 and UF line 154 drive fluidto the inlets of balance chambers 50 a and 50 b. In an HHD therapy fluidexits the valved outlets of balance chambers 50 a and 50 b to either adialyzer or the drain as described above. As before, balance chambers 50operate as intermediate metering devices that meter a like volume offluid to the drain and the dialyzer. Any of the methods for controllingultrafiltration described above can be used with flexible sheetingcassette 10 e. For example, a number of strokes of balance chamber 50can be dedicated UF strokes, in which spent fluid is pumped into bothhalves of balance chambers 50 a and 50 b. Alternatively, a separate UFbalance chamber can be provided.

As seen in FIGS. 21A and 21E, fresh dialysate is pumped from one of thesupply bags through a respective supply line 18 a to 18 e, into amanifold 162 and a dialysate pumping tube 148, which operates with aperistaltic dialysate pump actuator. The peristaltic dialysate pumppumps fresh dialysate through inlet connector 16, through integratedinline fluid heating pathway 42 b, and into one of the balance chambers50 a or 50 b. Any air egressing from the heated solution is allowed tovent through vent 44. In an embodiment, cassette 10 e is mountedvertically as shown in FIGS. 21A and 21E, such that air automaticallyrises to the top of cassette 10 e and is released through air vent 44and vent line 164 (FIG. 21E). This reduces the number valve actuatorsand seats as discussed above in connection with cassettes 10 a to 10 c.That is, any air is purged automatically without having to shutdown thenormal operation of the machine.

The pumping of fresh dialysate into an inlet compartment of one ofbalance chambers 50 a and 50 b causes a like amount of spent fluidalready residing in that balance chamber to be pumped via drainline 24to drain. At the same time, the UF pump actuator operating with UF pumpline 154 pumps spent fluid from the dialyzer, through from-patient line152 b, into the inlet compartment of the other of balance chambers 50 aand 50 b. Such action causes a like volume of fresh fluid to be pumpedthrough patient connector 62 a and to-patient line 152 a to thedialyzer.

As seen in FIG. 21A, a tubing organizer 168 is provided to hold supplylines 18 a to 18 e, drainline 24, vent line 164, to-dialyzer line 152 aand from-dialzyer line 152 b in an organized manner and enable cassette10 e and associated tubes to be mounted readily. FIG. 21A also showsdarkened areas 188 cooperating with manifold 162. Darkened areas 188indicate portions of the associated tubes that are pinched closed toselectively allow fresh dialysate to be pulled from a desired supply bag12 and spent dialysate to be pumped to drain bag 14 or one of the supplybags 12 being used as a drain bag.

Referring now to FIGS. 21C ad 21D, a number of additional features offlexible sheeting cassette 10 e are illustrated. The schematic side viewof FIG. 21D illustrates that sheets 74 a, 74 b and 74 c are formed froma single sheet of material, which is folded twice to produce the threelayers 74 (referring collectively to layers 24 a to 24 c). This allowsthe number of outer edge seams or seals to be reduced and also helpswith the alignment of separate layers 74 a to 74 c. It should beappreciated that any of the flexible sheeting cassettes described hereincan be formed using a single folded sheet, two sheets with one fold orthree separate sheets, etc.

FIGS. 21C and 21D also show first weld areas 190 a in which only firstsheet 74 a is welded to or otherwise fixed to sheet 74 b. Weld areas 190b are also shown in which all three sheets 74 a to 74 c are welded oradhered together. FIG. 21C also shows third areas 190 c in which onlythe second layer 74 b is welded to or otherwise fixed to third layer 74c. This selective welding enables cassette 10 e to be made efficiently.Welding of three sheets does not have to be made in areas in which onlytwo sheets need to be welded together. However, the three sheets can bewelded or otherwise attached in areas in which it is required to do so.In general, two layer welds or glue joints 190 a and 190 c are requiredwhen flow in one layer is desired but not in another layer. In analternative embodiment, three layer welds 190 b (except for peripherythree layer welds and three layer welds for inlet and outlet ports) areeliminated and replaced with the compression seals described below inconnection with FIGS. 24A, 24B, 25A, 25B, 26A, 26B and 28.

In FIG. 21C, selective welding occurs in areas associated with balancechambers 50 a and 50 b. FIG. 6 provides further information on how threesheeted balance chambers 50 can be welded together. Serpentine pathway42 b is formed from a three sheet weld. This enables fluid heatingpathway 42 b to extend spatially efficiently between sheets 74 a and 74b and sheets 74 b and 74 c.

FIGS. 21C and 21D illustrate that the fluid travels between differentlayers or sheeting pairs using apertures 96 made in desired places inmiddle sheet 74 b. Fluid for example enters single supply connector 16in a first pathway between sheets 74 b and 74 c. An aperture 96 aenables the fluid to travel into a portion of fluid heating pathway 42 blocated between sheets 74 a and 74 b, in which it is heated a firsttime. Next, the fluid moves through an aperture 96 b into a secondportion of fluid heating pathway 42 b located between sheets 74 b and 74c. Any air egressing the heater solution is vented through the top ofcassette 10 e via event 44. Next, the heated fluid enters the balancechamber area, which uses all three sheets 74 a to 74 c in oneembodiment. The fresh fluid leaves through a balance chamber compartmentlocated between sheet 74 b and 74 c to the dialyzer through two patientconnector 62 a. Spent fluid returns from the dialyzer to cassette 10 evia from patient connector 62 b into a balance chamber compartmentlocated between sheets 74 a and 74 b. The spent fluid is sent to drainvia drain connector 22 located between sheets 74 a and 74 b.

Referring now to FIGS. 21B and 21F, one embodiment of a blood cassette150 used with HD, HHD and HF is illustrated. Blood cassette 150 is alsomounted vertically as illustrated in one embodiment. Cassette 150includes a rigid portion 170 having a rigid housing 172 and a flexiblemembrane 174 made of any of the materials discussed above attached tohousing 172. Rigid portion 170 is made from a suitable material, such aspolyvinyl chloride (“PVC”), acrylic, ABS, polycarbonate, polyolefinblends. Housing 172 includes or defines a from-patient port 176, ato-patient port 178, a saline port 180, a vent 44, a to-dialyzer port182 and a from-dialyzer port 184. As seen FIGS. 21B and 21F ports, suchas ports 178 and 180, port 184 and vent 44 can be formed in differentrelative locations along housing 172.

FIG. 21B illustrates valve seats 28 x to 28 z operating with thefrom-patient line, to-patient line and the saline line, respectively. Aperistaltic pump actuator operates with blood pump line 166 to pumpblood from the patient, to cassette 150 to the dialyzer, back tocassette 150 and then back to the patient. Fluid received from thedialyzer enters an air separation chamber 192 before being returned tothe patient. Blood 186 collects at the bottom of air separation chamber,while any air in the blood raises to the top of air separation chamber192. Air separation chamber 192 can further include a vent 44, such as ahydrophobic membrane, which allows air to be purged from cassette 150.

The operation of blood cassette 150 of FIG. 21F is similar to theoperation described in connection with FIG. 21B. Here, however, valveseat 28 y operates with to-dialyzer line connected to to-dialzyer port182. Valve seat 28 x controls the fluid entering cassette 150 from thepatient as shown in FIG. 21B. Valve seat 21 z controls the flow ofsaline into the cassette. Air separation chamber 192 operates as before,in which air at the top of chamber 192 can exit cassette 150 via vent44. Blood at the bottom of air separation chamber 192 flows to thepatient through to-patient port 178. FIG. 21F further illustrates that aflexible sheet 174 is welded or adhered to rigid portion 172 of housing170. The flexible sheet 174 enables a valve actuator to press valveseats 28 x to 28 z to open/close a respective fluid flow path. Asfurther illustrated in FIG. 21F, blood cassette 150 includes or providessensing areas 194 a and 194 b to sense a parameter of the blood, such asarterial pressure, venous pressure or blood temperature.

Cassette 150 illustrates components associated with a blood cassetteused with HD, HHD, HF, HDF and any combination thereof as described inthe parent application. As seen, the blood cassette can be provided as aseparate cassette 150 installed separately from a dialysate cassette 10a to 10 b. Alternatively, the components of the blood cassette areintegrated with any one of dialysate cassettes 10 disclosed herein.

Referring now to FIG. 21G, a top view of hemodialysis machine 100 eillustrates one embodiment for mounting cassette 10 e, the varioussupply bags 12 and drain bag 14. Cassette 10 e can be placed on a anglerelative to the top of machine 100 e, so as to create at least a slightvertical component to the mounting of cassette 10 e for venting purposesdiscussed above. Supply bags 12 and drain bag 14 are supported by thetop of machine 100 e and are connected fluidly to cassette 10 e beforeor after the cassette is mounted to machine 100 e. Machine 100 eincludes the user interface 196, which enables the patient or caregiverto begin, control and monitor therapy. User interface 196 can use atouch screen overlay operable with a touch screen controller and/ormembrane switches as desired.

Referring now to FIGS. 22A to 22D, a further alternative system 100 femploying an alternative flexible sheeting cassette 10 f is illustrated.System 100 f is well-suited to perform hemodialysis, such as homehemodialysis. Here, system 100 f also uses a second blood cassette,which can be similar to or the same as blood cassette 150 describedabove. FIG. 22A illustrates one embodiment for loading the cassettes 10f and 150 into machine 100 f. Here, the dialysate components are locatedon one side of user interface 196, while the blood components arelocated on the other side of user interface 196. This configurationmakes loading the cassettes relatively easy for the user and also allowsthe valve and pump actuators and heater located within machine 100 e tobe mounted efficiently, reducing the overall size of machine 100 f.

In machine 100 f, cassette 10 f is positioned vertically, which isadvantageous for air purging purposes described above. Machine 100 fincludes two peristaltic pump actuators 90, one of which drives fluidthrough a dialysate tube, while the other drives fluid through a UFtube, similar to the arrangement described above for cassette 10 e. Aseparate heater bag 40 described above in connection with FIG. 1 extendsto the right from a rigid housing portion 200 of cassette 100 f. Rigidhousing portion 200 as shown in more detail below defines flow paths andassociated valve seats. Accordingly, the valve actuators of machine 100f are located behind rigid cassette portion 200 of cassette 10 f A plateheater or other type of heater is located behind heater bag 40. A dualbalance chamber flexible membrane component 198 of cassette 10 f residesbeneath rigid portion 200. As discussed herein, peristaltic pumpactuators 90 drive fresh and spent fluid alternatively through the inletcompartments of balance chambers 50 a and 50 b. A hinged door 202enables cassette 10 f, including its rigid portion 200, balance chambercomponent 198 and heater bag 40 to be inserted and removed readily frommachine 100 f.

Referring now to FIG. 22B, a more detailed view of cassette 10 f isillustrated. As discussed, cassette 10 f includes a rigid portion 200connected fluidly to a separate heater bag 40 and a balance chamber unit198. Cassette 10 f therefore differs from cassette 10 e in that theheating and balance chamber functions are done via the flexible sheetingmembranes, while valve actuation is performed using a rigid member 200in combination with a flexible sheet 202. Valve actuators, e.g.,spring-loaded closed, pneumatically operated open actuators, operatewith valve seats 28 to open and close selected flow paths as desired.Cassette 10 f also includes separate peristaltic pumping tubes 148 and154 described above in connection with cassette 10 e. Heater bag 40includes a serpentine heating pathway (not illustrated) and communicateswith rigid member 200 via to-and from-heater lines 38 a and 38 b,respectively. Balance chamber unit 198 also communicates with rigidvalve member 200 via port connectors and tubes as illustrated.

Balance chamber unit 198 is illustrated in more detail in FIGS. 22C and22D. Balance chamber unit 198 is similar to the flexible sheetingbalance chamber 50 described above in connection with FIGS. 20A to 20D.Here, unit 198 provides two balance chambers 50 a and 50 b, which aremade of flexible sheets 74 a to 74 c, fresh fluid tubes 156 and spendfluid tubes 158. As seen best in FIG. 22D, each compartment of balancechambers 50 a and 50 b communicates with only one of fresh tube 156 orspent 158. Fresh tube 156 communicates with a first balance chambercompartment located between sheets 74 a and 74 b, while spent tube 158communicates fluidly with a second balance chamber compartment locatedbetween sheets 74 b and 74 c. Balance chambers 50 a and 50 b eachinclude seals 72 e, 72 f and 72 l as described above in connection withFIGS. 20A to 20D.

FIG. 22D illustrates that sheets 74 a to 74 c have semicircular bends76, similar to that of balance chamber 50 of FIGS. 20A to 20D. Bends 76can be preformed or at least partially preformed, e.g., viathermoforming. Alternatively, bends 76 are formed during the process ofsealing sheets 74 a to 74 c about tubes 156 and 158. Bends 76 are madeoutwardly in outer sheets 74 a and 74 c. Bends 76 in middle sheet 74 balternate direction for each of balance chambers 50 a and 50 b. As seen,each tube 156 and 158 has a single sheet 74 a or 74 c welded on one sideand two sheets 74 a or 74 c in combination with middle sheet 74 b weldedon its other side. In one embodiment, tubes 156 and 158 are welded tomiddle sheet 74 b first. Outer sheets 74 a and 74 c are then welded tomiddle sheet 74 b and the exposed parts of tubes 156 and 158.

In operation, fresh fluid enters and leaves through tube 156. Spentfluid enters and leaves through tube 158. That is, there is not aseparate inlet and outlet tube for each balance chamber compartment isthe case with balance chamber 50 of FIGS. 20A to 20D, which has twofresh tubes 156 a and 156 b and two spent tubes 158 a and 158 b. Rather,the same tube acts as the fresh or spent fluid inlet and fluid outletfor its compartment. Valves and flow paths are configured within rigidmember 200 to direct the flow into or out of balance chambers 50 a and50 b as desired.

Fresh fluid entering the fresh balance chamber compartment betweensheets 74 a and 74 b through tube 156 causes middle sheet 74 b to dispela like amount of spent fluid from spent compartment between sheets 74 band 74 c through spent tube 158. While this occurs in one of balancechambers 50 a and 50 b, spent fluid enters spent compartment betweensheets 74 b and 74 c of the other balance chamber, flexing middle sheet74 b to dispel a like amount of fresh fluid from fresh compartmentbetween sheets 74 a and 74 b through fresh tube 156. The sequence isthen reversed. In this manner, an at least semicontinuous flow of fluidis sent to the patient or dialyzer and to drain.

Referring now to FIG. 23, a further alternative cassette is illustratedby cassette 10 g. Cassette 10 g is a simplified version of cassette 10e. Cassette 10 g includes supply lines 18 a to 18 e, drainline 24,dialysate pump tube 148, return pump tube 154, inline fluid heatingpathway 42 b, vent 44, vent line 164, to-patient connector 62 a,to-dialyzer line 152 a, and from-dialyzer line 152 b. The primarydifference between cassette 10 g and cassette 10 e is that balancechambers 50 a and 50 b used with cassette 10 e are not used withcassette 10 g. That is, volumetric control of fluid is not performedusing matched flow equalizers or balance chambers 50 a and 50 b withflexible sheeting cassette 10 g. Instead, another method is used, suchas via gravimetric or weight control of fluid delivered and removed fromthe patient or via a flow management system (“FMS”) used with aHomeChoice® dialysis machine marketed by the assignee of the presentapplication. The body of sheeting cassette 10 g can include valve seatand flow paths as needed to direct flow in a desired manner.Alternatively, flow can be controlled by clamping and unclamping thetubes connected to cassette 10 g, in which case cassette 10 g servesprimarily as a fluid heating pathway. The flow paths, valve seats andfluid heating pathway 42 b can be provided via two sheets 74 a and 74 bor three sheets 74 a to 74 c as has described herein or can have a rigidcomponent, such as rigid frame.

Referring now to FIGS. 24A and 24B, a further alternative system 100 hemploying flexible membrane cassette 10 h is illustrated. System 100 his well-suited to perform hemodialysis, such as home hemodialysis.System 100 h uses a blood cassette, such as cassette 150. FIG. 24A showssystem 100 h without cassette 10 h loaded. FIG. 24B shows system 100 hwith cassette 10 h loaded.

Cassette 10 h is simplified to a large extent because mating die plates210 a and 210 b of machine 100 h clamp together around cassette 10 h toform the balance chamber portion, fluid heating pathways and other fluidflow paths of the cassette as installed. That is, the balance chamberportion, pathways, etc., do not have to preformed in cassette 10 h priorto loading. The closing of door 202 against wall 220 of machine 100 hinstead forms the fluid-tight passageways mechanically. Cassette 10 h ispreformed as a pouch 212 as seen in FIG. 25B, which is made of threesheets 74 a to 74 c or two sheets 74 a and 74 b as necessary to form thedesired components. Pouch 212 is connected fluidly to to-dialyzer line152 a, from-dialyzer line 152 b, vent line 164, inlet connector 16,supply lines 18 a to 18 f and drainline 24 as seen further in FIG. 24 b.

Die plate 210 a is formed hinged door 202. Matching die plate 210 b isformed on wall 220 of machine or system 100 h. In the illustratedembodiment, die plate 210 a includes heating pathway forming ridges 214a that mate with heating pathway forming ridges 214 b of die plate 210b. Die plate 210 a includes balance chamber forming ridges 216 a thatmate with balance chamber forming ridges 216 b of die plate 210 b. Dieplates 210 a and 210 b also form or include tube/connector acceptinggrooves 218 a and 218 b, respectively, which secure tubes 152 a, 152 b,and 164 in place when door 202 is closed without crimping or closing thetubes. Die plates 210 a and 210 b alternatively or additionally form anyother additional flexible sheeting apparatus discussed herein, such asvolumetric pumping portions 70, UF meter portions internal flow paths26, valve seats 28, etc.

At least one of die plates 210 a and 210 b is integrated with componentactivation, such as, a heater, pump actuator, balance chamber actuatorand/or valve actuator. Heating is accomplished via electrical resistanceplate heating, inductive heating, radiant heating and/or ultrasonicheating. FIG. 25A shows one embodiment of an in-line electricalresistance or plate heater configured to heat a fluid heating pathwayformed by mechanical clamping. FIG. 25B shows a separate heater havingheating pathway forming clamshell sides, the teachings of which are alsoapplicable to system 100 h. FIGS. 26A and 26B show a balance chamberportion of a flexible sheeting cassette formed via mechanical clamshellridges, which can be activated pneumatically, mechanically,hydraulically or in the illustrated case electromagnetically. FIG. 28shows a volumetric pump portion of a flexible sheeting cassette formedvia mechanical clamshell ridges, which can also be activatedpneumatically, mechanically, hydraulically or in the illustrated caseelectromagnetically. System 100 h can integrate any of thesetechnologies into one or more of die plates 210 a and 210 b.

In the illustrated embodiment, pouch 212 is shown without any innerseams, except those needed to seal to connectors, e.g., connector 16,and/or tubes 152 a, 152 b and 164. It is contemplated to alternativelyprovide internal safety seams to mitigate damage due to leaking. Forexample, a seam could be provided to separate the fluid pathway portionof pouch 212 from the balance chamber portion of the pouch. Another seamcould be provided to separate or isolate balance chamber portion 50 afrom balance chamber portion 50 b, and so on. The safety seams can haveany desired shape or pattern but can advantageously be simpler than theshape or pattern needed to form the flow component portions outright.Safety seams can be between sheets 74 a and 74 b, 74 b and 74 c andbetween all three sheets 74 a to 74 c.

It is alternatively expressly contemplated to form the two sheet seals,for instance, between sheets 74 a and 74 b or 74 b and 74 c, using thebonding or welding methods described above to form the actual flowcomponents having two-sheet seals. Mechanical clamshell sealing here isused anywhere that a seal between all three sheets 74 a to 74 c isneeded. Here again, the overall number and pattern of the welds or bondsshould be lessened and simplified, respectively.

Referring now to FIG. 25A, the heating portion of cassette 10 h formedby mechanical clamping heating pathway forming ridges 214 a and 214 b isillustrated. Cassette 10 h as shown in FIG. 25B includes a pouch 212,which receives fresh dialysate via fresh fluid inlet connector 16.Ridges 214 a and 214 b form an inline fluid heating pathway 42 b, whichreceives the fresh fluid from inlet connector 16. Inline fluid heatingpathway 42 b serpentines back and forth as shown above to collect heat.Heated dialysate leaves through internal pathway 222, which is alsoformed via mechanical clamping. Heated fluid through pathway 222 travelsto balance chambers 50 a and 50 b or to a volumetric pump 70 forexample.

In the illustrated embodiment clamping ridges 214 a and 214 g are alsoheating elements, for example, aluminum plate heating elements. Furtherelements 224 a and 224 b are connected to door 202 and machine wall 202,which can also be electrical resistance elements. In one implementation,the heat actuator is a power supply that supplies power, e.g., 200watts, to resistance elements 214 a, 214 b, 224 a and 224 b. Alternativetypes of heat actuators include inductive, radiant, connective,ultrasonic or a combination of heating types. Clamping ridges 214 a and214 b can but do not have to be heat providing.

As illustrated, the heater using whatever type(s) of heat transfer iscapable in one embodiment of heating dialysate starting from atemperature of about five to about thirty ° C. to a temperature of aboutthirty-seven ° C. or body temperature and at a flowrate of from zero toabout three-hundred ml/min. A controller (not illustrated) withinmachine 100 h controls a duty cycle or power on/power off cycle in oneembodiment to accommodate different starting dialysate temperatures anddifferent dialysate flowrates. The controller can be a delegate orsubordinate processor operating with a supervisory processor and asafety processor. An outflow fluid temperature monitor 226 senses thetemperature of dialysate leaving fluid heating pathway 42 b and providesfeedback to the controller to increase or decrease the duty cycle asneeded to achieve the desired outflow temperature.

Referring now to FIG. 25B, a separable fluid heater 240 employingmechanical clamping to create a fluid heating pathway (e.g., likepathway 42 a of FIGS. 1 and 3) within the separate heater 240 isillustrated. Separate fluid heater 240 can be used for example in system100 a of FIG. 1, system 100 c of FIG. 3, and cassette 10 f of FIGS. 22Aand 22B. Heater 240 employs any of the types of heating in anycombination discussed herein.

A fluid heating pouch 230 is connected to heater lines 38 a and 38 bthrough any method described herein. Materials for pouches 212, 230include any of those for sheets 74 a to 74 c. Materials for tubes 38 aand 38 b include any of those for the tubing described herein. As seen,heating pouch 230 as formed is simpler than fluid heating pathway 42 aof separate heater 40 of FIGS. 1 and 3.

Heater 240 in the illustrated embodiment includes a clamshellconfiguration, in which first and second heating enclosures 242 and 244are connected hingedly together. When closed, heating path formingridges 214 a and 214 b of enclosures 242 and 244, respectively, mate andclamp pouch 230. Enclosures 242 and 244 also form or include grooves 218a and 218 b, respectively, which except lines 38 a and 38 b,respectively, allowing enclosures 242 and 244 to fit flushly togetherwithout crimping those lines.

Ridges 214 a and 214 b may or may not themselves be heating elements asdescribed above in connection with FIG. 25A. Enclosures 242 and 244 inan embodiment each include a heating plate 246 a and 246 b,respectively. Heating plates 246 a and 246 b heat fluid within thecrimped fluid heating pathway, for example, according to thetemperatures and flowrates described above in connection with FIG. 25A.

Referring now to FIGS. 26A and 26B, an alternative apparatus and methodfor operating a balance chamber 250 is illustrated. One primarydifference illustrated by FIG. 26A is that balance chamber 250 is drivenmagnetically and not via a separate pump as has been discussedpreviously. Middle sheet 74 b includes outer plies 74 d and 74 e, whichsandwich a layer ferromagnetic material 252, such as carbon or iron.Ferromagnetic material 252 is thin enough to allow middle sheet 74 b toflex back and forth as necessary within a chamber formed by chamberforming members 102 a and 102 b. Outer plies 74 d and 74 e can be of anymaterial listed above for sheets 74 a to 74 c. Alternatively,ferromagnetic material 252 is impregnated or interspersed, e.g., as apowder or grain, into a single ply sheet 74 b. In any case, middle,moving sheet 252 needs to be compatible with sterile or near sterilemedical fluids.

Balance chamber 250 is shown in operation with a portion of a dialysismachine 100 (e.g., 100 a, 100 c, 100 e, 100 f and 100 h) operating witha cassette 10 (e.g., cassette 10 a, 10 c, 10 e, 10 f and 10 h,respectively). Dialysis machine 100 includes or defines first and secondchamber forming members 102 a and 102 b. For example, one of members of102 a or 102 b is stationary and configured to accept flexible sheetingcassette 10 (e.g., formed in wall 220 of machine 100 h), while the otherof chamber forming members 102 a or 102 b is part of a door (e.g., door202) that is closed onto the opposing side of flexible sheeting cassette10 after it has been loaded into dialysis machine 100.

Electromagnets 254 a and 254 b in the illustrated embodiment areembedded within members 102 a and 102 b, respectively, creating amagnetic field around the chamber, which can be modulated and polarizedto pull ferromagnetic sheet 74 b to upper sheet 74 a or lower sheet 74 cof cassette 10. Electromagnets 254 a and 254 b are alternatively coiledaround spherical chamber-creating members 102 a and 102 b, respectively,and are in any case provided with enough mass to operate balance chamber250 as discussed below.

Electromagnets 254 a and 254 b are each connected via leads 256 and 258to a controller 248. Controller 248 in one embodiment is a delegate orsubordinate controller or printed circuit board (“PCB”) that operateswith a supervisory processor and a safety processor. Controller 248 inone embodiment also controls the valves operating with valve seats 28 jto 28 m (See FIGS. 1 and 3), which switch in synchronization with theswitching of electromagnets 254 a and 254 b.

To polarize electromagnet 254 a, controller 248 causes the leads 256 and258 leading to electromagnet 254 a to power that electromagnet. Topolarize electromagnet 254 b, controller 248 causes the leads 256 and258 leading to electromagnet 254 b to power that electromagnet. Whenelectromagnet 254 a is energized, ferromagnetic sheet 74 b is pulled tothe top of balance chamber 250. When electromagnet 254 b is energized,ferromagnetic sheet 74 b is pulled to the bottom of the chamber. In thismanner, balance chamber 250 is self-powering or self-operating andprovides a pumping function in addition to a metering function. Aseparate pump is not needed.

It is also contemplated that magnetically doped middle layer 74 b alsoallows for the measurement of position of the layer. By oscillating thepower to electromagnetic coils 254 a and 254 b, it is possible to readthe current generated by the inertial movement of the layer in theelectromagnetic coil when the coil is off. This information relates toor is dependent on the velocity of the middle, magnetically doped layer74 b. By integrating the velocity information it is possible to reliablydetermine position. This information can be used for determiningflowrate out of or into the chamber and to determine when the chamberstroke has finished.

In the illustrated embodiment, chamber forming members 102 a and 102 beach define or include a port 104 to which a tube (not illustrated) isreleasably or permanently secured via any of the methods and embodimentsdiscussed herein. In an embodiment, after cassette 10 is loaded intomachine 100, a static negative pressure or vacuum is drawn on ports 104,pulling first and third plies or sheets 74 a and 74 c against the innerat least substantially spherically shaped cavities defined by first andsecond members 102 a and 102 b. Flexible sheets 74 a to 74 c are made ofa suitably stretchable, complaint, non-magnetic and leak-free material.

Although members 102 a and 102 b are shown defining at leastsubstantially spherical shapes, other suitable cross-sectional shapesmay be used, such as substantially triangular or substantiallytrapezoidal shapes. Further, although not illustrated, members 102 a and102 b can define air channels that extend radially from ports 104 invarious directions to help spread the vacuum across a larger surface ofplies 74 a and 74 c. Once sheets 74 a and 74 c are pulled via vacuumagainst the inner surface of chamber forming members 102 a and 102 b,respectively, balance chamber 50 is ready for operation.

In one alternative embodiment, sheets 74 a and 74 c are rigid orsemi-rigid and preformed having the, e.g., semicircular, chamber shape,making ports 104 and associated negative pressure unnecessary. Inanother alternative embodiment, electromagnets 254 a and 254 b andferromagnetic sheet 74 b are employed with a balance chamber that isre-used, i.e., is not disposable, so that outer sheets 74 a and 74 c arenot needed. That is, magnetic actuation can be used with any type ofbalance chamber and is expressly not limited to a cassette-based orflexible sheeting cassette-based application as shown here.

FIG. 26A illustrates a state of operation in which no fluid has beendelivered to balance chamber 250. In the illustrated embodiment, valveseat 28 l is shown operating with a valve actuator 106, which is part ofmachine 100. Here, positive air pressure is applied to the port ofactuator 106 to force a plunger 108 to compress valve seat 28 l againstsecond sheet 74 b, closing balance chamber outlet 58 a. Actuator 106includes an o-ring seal 110, which creates a sliding seal betweenplunger 108 in the inner, e.g., cylindrical housing of valve actuator106. To open balance chamber outlet 58 a, a negative pressure is appliedto port 106, pulling plunger 108 upwards against stop 112, enablingfluid to open seat 28 l and flow outwardly from upper balance chambercompartment 54 a through balance chamber outlet 58 a.

In operation, to fill upper balance chamber compartment 54 a, plunger108 is pressurized, closing valve seat 28 l and balance chamber outlet58 a. A similar valve actuator and plunger closes balance chamber inlet56 a. Electromagnet 254 a is energized, pulling sheet 74 b against uppersheet 74 a. Next, the valve actuator and plunger operating with balancechamber inlet 56 a is opened, electromagnet 254 a is de-energized,electromagnet 254 b is energized, pulling sheet 74 b fully across thechamber and against lower sheet 74 c, creating a vacuum and fillingupper balance chamber compartment 54 a.

To empty upper balance chamber compartment 54 a and fill lower balancechamber compartment 54 b, the valve actuator and plunger operating withbalance chamber inlet 56 a is closed, plunger 108 is pulled against stop112, opening valve seat 28 l and balance chamber outlet 58 a,electromagnet 254 b is de-energized, electromagnet 254 a is energized,pulling sheet 74 b fully across the chamber and against upper sheet 74a, dispelling fluid from balance chamber compartment 54 a, throughbalance chamber outlet 58 a and simultaneously creating a vacuum withinbalance chamber compartment 54 b, filling such chamber. The cycle isthen reversed using second balance chamber inlet 56 b and second balancechamber outlet 58 b (See FIG. 1) to dispel fluid from balance chambercompartment 54 b and simultaneously fill balance chamber compartment 54a.

Because the volume defined by compartments 54 a and 54 b is fixed andbecause second sheet 74 b is pushed all the way against upper and lowersheets 74 a or 74 c in each half stroke, the same volume of fluid isoutputted through balance chamber outlets 58 a and 58 b in each halfstroke. In this manner fresh and spent fluid balancing and UF removalcan be readily and accurately controlled.

It is also contemplated to impregnate plungers 108 with a ferromagneticmaterial and open and close valve seats 28 electromagnetically.

Referring now to FIG. 26B, FIG. 26A is rotated ninety degrees about anaccess through ports 104 to show one embodiment for creating balancechamber seals via mechanical clamping crimping. Chamber forming members102 a and 102 b each define or include a balance chamber crimping ridgeor ring 216 a and 216 b (described above in connection with FIGS. 24Aand 24B). Rings 216 a and 216 b in an embodiment extend around thecircumference of balance chamber 50 or 250, except to allow for inletand out let paths 56 and 58. Rings 216 a and 216 b crimp together toseal sheets 74 a to 74 c mechanically enough to withstand the positiveand negative pressures and variations of same within the chamber.Clamping rings 216 a and 216 b operate with any type of balance chamberoperation, e.g., via separate pump or electromagnetic operation.

An outer safety ring seal 72 m may be provided optionally. Seal 72 m isformed via any of the techniques discussed herein. It serves to mitigatethe damage from any dialysate escaping the mechanical seal formed bymechanical rings 216 a and 216 b. It also allows for tolerance inaligning cassette 10 within machine 100.

Referring now to FIG. 27, one embodiment of a magnetically drivenbalance tube 260 is illustrated. A balance tube is discussed inconnection with FIG. 45 of the parent application. As discussed in theparent application, balance tube 260 here includes a separator 262,which functions similar to flexible membrane 74 b of balance chamber250. In the illustrated embodiment, separator 262 is a ball or sphericalobject that moves snuggly within a cylindrical housing 264. A pair ofcaps 266 and 268 are provided on either end of cylindrical housing 264.Caps 266 and 268 seal to cylindrical tubing 264 via outer O-rings 270.Separator or ball 262 seals to caps 266 and 268 via inner O-rings 272.In an alternative embodiment, caps 266 and 268 are permanently orhermetically sealed to cylindrical tube 264. Ports 274 and 276 areformed integrally with or are attached to caps 266 and 268,respectively. Ports 274 and 276 seal to mating tubes via any mechanismknown to those with skill in the art.

Separator 262 is impregnated with a ferromagnetic material, such ascarbon or iron. For example, a carbon core could be covered with a shellmade of a medically safe material. Electromagnets 254 a and 254 b are inone embodiment embedded within caps 266 and 268, respectively, creatinga magnetic field around separator 262, which can be modulated andpolarized to pull ferromagnetic separator 262 to upper cap 266 or lowercap 268. Electromagnets 254 a and 254 b are each connected via leads 256and 258 to a controller 248 described above. Electromagnets 254 a and254 b are alternatively located outside of caps 266 and 268 and coiledinstead around caps 266 and 268 and potentially end positions of tube264. Here, the magnets can be housed within the machine as opposed tobeing located with in tube 260.

To polarize electromagnet 254 a, controller 248 causes the leads 256 and258 leading to electromagnet 254 a to power that electromagnet. Topolarize electromagnet 254 b, controller 248 causes the leads 256 and258 leading to electromagnet 254 b to power that electromagnet. Whenelectromagnet 254 a is energized, ferromagnetic separator 262 is pulledto cap 266. When electromagnet 254 b is energized, ferromagneticseparator 262 is pulled to cap 268. The movement of ball 262 pushes outand pulls in fresh/spent or spent/fresh fluid through port 274 or 276upon each stroke. In this manner, balance tube 260 is self-powering orself-operating and provides a pumping function in addition to a meteringfunction. A separate pump is not needed. As discussed above,magnetically impregnated separator 262 allows for its position to bedetermined within housing 264

In an embodiment, cylindrical tube 264 is translucent or transparent, sothat an optical sensor can detect if ferromagnetic ball or separator 262has properly reached the end of travel. Ultrasonic or other types ofsensors may be used alternatively. Ferromagnetic ball or separator 262is sized to fit snuggly but smoothly within the interior of cylinder264. A small amount of mixing between fresh and effluent fluid may occurwithout substantially affecting the performance of the system. In analternative embodiment, a cylindrical piston type separator is provided.In either case, ferromagnetic separator 262 may have additional sealingapparatus, such as wipers or deformable flanges that help to enhance thesliding or rolling seal as the case may be.

Balance tube 260 may be made of plastic or other suitable material. Inan embodiment, balance tube 260 is a disposable item, which may beformed integrally with cassette 10 or attached to the cassette viatubing. O-rings and fittings may not be necessary if injection moldedcaps or assemblies are used. In addition, sensors such as ultrasonic oroptical sensors, for the positioning of the separator can eliminate theneed for sealing at the end of the tube.

Referring now to FIG. 28 an electromagnetically controlled volumetricpump 280 is illustrated. Volumetric pump 280 is shown operating with adialysis machine 100, such as machine 100 b (FIG. 2), which uses acassette 10, such as cassette 10 b (FIG. 2). Pump 280 can operate out ofphase with a second electromagnetically controlled volumetric pump 280in a manner discussed herein.

Machine 100 includes first and second pump chamber forming members 114 aand 114 b, which define the shape of the volumetric pump 280. Cassette10 is configured to be loaded within the machine 100 such that acircular flexible membrane portion of cassette 10 is in alignment withthe spherically shaped chamber defined by pump chamber forming members114 a and 114 b. Although the spherical shape shown in FIG. 28 is onesuitable shape, other shapes could be defined for volumetric pump 280,such as a trapezoidal or triangular shape. Also, valve seats 28 q and 28s are aligned with valve actuators 106 as shown. Valve actuators 106operate as described above in connection with FIG. 7 and include aplunger 108, which slides back and forth within the actuator body.

Pump 280 uses first and second flexible sheets 74 a and 74 b. Sheets 74a and 74 b are each impregnated with a ferromagnetic material 252, suchas an inner carbon or iron layer. Electromagnets 254 a and 254 b areembedded within pump chamber forming members 114 a and 114 b,respectively, creating a magnetic field around sheets 74 a and 74 b,which can both be energized to pull ferromagnetic sheets 74 a and 74 bapart to upper and lower members 114 a and 114 b, respectively.Alternatively, only one of electromagnets 254 a and 254 b is energized,pulling both sheets 74 a and 74 b towards that electromagnet.Electromagnets 254 a and 254 b are each connected via leads 256 and 258to a controller 248 as described above. They can alternatively belocated outside of an winding around members 114 a and 114 b.

In an initial state (shown in FIG. 28), electromagnet 254 b is powered,which pulls first and second flexible sheets 74 a and 74 b to conformwith the inner surface of lower chamber forming member 114 b. Initially,a positive pressure is applied to both valve actuators 106, closingvalve seats 28 q and 28 s. Again, valve actuators 106 can be anycombination of pneumatically, mechanically, electrically and/orelectromagnetically operated. As seen in FIG. 28, dialysate or medicalfluid (including blood) 116 is pressurized against valve seat 28 q, butis precluded from entering into the sealed chamber of volumetric pump280.

In a second state, electromagnet 254 b continues to be powered as is thepositive pressure applied to valve actuator 106 at valve seat 28 s. Anegative pressure is applied to valve actuator 106 at valve seat 28 q,which pulls and holds plunger 108 to and against stop 112, allowingfluid 116 to flow through pump inlet pathway 66 b and into the chamberof volumetric pump 280. The force of fluid 116, e.g., via gravity may beenough to cause first flexible member 74 a to be pushed against innersurface of upper pump chamber forming member 114 a. Alternatively oradditionally, electromagnet 254 a is powered to pull first flexiblesheet 74 a against the inner surface of upper member 114 a. This actioncauses a vacuum, which pulls fluid 116 into the pump chamber.

In a third state, valve seat 28 q is closed, while valve seat 28 s isopened. Power at electromagnet 254 b is maintained, so that sheet 74 bcontinues to be pulled against member 114 b. Power is removed fromelectromagnet 254 a causing electromagnet 254 b to pull upper flexiblesheet 74 a against lower flexible sheet 74 b at member 114 b, which inturn causes fluid 116 to be pushed out of the at least substantiallyspherical chamber of volumetric pump 280, through pump outlet pathway 68b, to its desired destination. First and second membranes 74 a and 74 bare now at the initial state shown in FIG. 28, so that pump 280 is ableto repeat the above described cycle as soon as valve seat 28 s isclosed.

Because the volume formed by the chamber of members 114 a and 114 b isknown and because the flexible sheets are moved repeatedly to the upperand lower surfaces of the chambers, the volume of fluid pumped with eachstroke is known and repeatable. Accordingly, a separate volumetriccontrol apparatus, such as balance chamber 50 or 250, is not needed. Thetotal volume of fluid pumped is equal to the volume of each strokemultiplied by the number of strokes. UF is controlled via one of themethods discussed above. As discussed above, magnetically impregnatedsheet 74 a and 74 b allow for their position to be determined withinchamber forming members 11245 and 114 b.

Many embodiments have been described herein for different flexiblesheeting cassettes having varying degrees and types of fluid flowcomponents and functionality. The parent application for thisapplication referenced herein includes many different embodiments forhemodialysis hemofiltration and hemodiafiltration systems. Inparticular, many embodiments are shown using dual dialzyers and a flowrestriction between the dialyzers, which causes both diffusive andconvective clearances associated with HHD. The flexible sheetingcassettes described herein may be used for each of the systems describedin the parent application, including but not limited to: (i) thevolumetric pump-based HCHDF systems of FIGS. 1, 4 and 5, which providediffusive and convective clearance; (ii) the volumetric pump-based HFsystems of FIGS. 6 and 7; (iii) the alternative volumetric pump-basedHDF system of FIG. 8; (iv) the volumetric pump-based regenerationsystems of FIGS. 9 to 11; (v) the peristaltic pump-based HDF and HFsystems of FIGS. 12 and 13; (vi) the co-current flow system of FIG. 14;the pneumatically controlled system of FIGS. 15 and 16; (vii) the singlebalance chamber systems of FIGS. 17 to 22; (viii) the torturous pathsystem of FIGS. 24 and 29, wherein the tortuous paths are formed betweenthe sheets or plies 74 a to 74 u in any of the manners described above;(ix) the dual balance chamber systems of FIGS. 25 and 26; (x) the weightmeasurement system of FIGS. 30 and 31; the enhanced convection of HDFfilter of FIG. 32; (xi) the linear tubing pump systems of FIGS. 38 to41; and (xii) the fluid heater of FIGS. 42 and 43.

It should be understood that various changes and modifications to thepresently preferred embodiments described herein will be apparent tothose skilled in the art. Such changes and modifications can be madewithout departing from the spirit and scope of the present subjectmatter and without diminishing its intended advantages. It is thereforeintended that such changes and modifications be covered by the appendedclaims.

The invention is claimed as follows:
 1. A hemodialysis systemcomprising: a dialyzer; a dialysate source; a dialysate pump; adialysate cassette operatively connected to the dialysate pump such thatthe dialysate pump can pump dialysate through the dialysate cassettewhen the dialysate cassette is in fluid communication with the dialysatesource, the dialysate cassette in fluid communication with the dialyzer;a blood pump; and a blood cassette operatively connected to the bloodpump such that the blood pump can pump blood through the blood cassette,the blood cassette including a rigid housing and a flexible membraneattached to the rigid housing, the housing including a from-patient tubeconnector, a to-patient tube connector, a to-dialyzer tube connector, afrom-dialyzer tube connector, and wherein the flexible membrane definesa valve seat for opening and closing a to-patient line of the bloodcassette, the to-patient line in fluid communication with the to-patienttube connector.
 2. The hemodialysis system of claim 1, which includes aninternal air separation chamber connected fluidly to the from-dialyzertube connector and the to-patient tube connector.
 3. The hemodialysissystem of claim 1, which further includes a tube connector for primingthe blood cassette.
 4. The hemodialysis system of claim 1, wherein theblood cassette is operably connected to the blood pump via a bloodpumping tube extending outside of the rigid housing, the blood pumpingtube connected fluidly to the from-patient tube connector and theto-dialyzer tube connector.
 5. The hemodialysis system of claim 1,wherein at least one of the tube connectors is a tube port.
 6. Thehemodialysis system of claim 1, wherein the to-dialyzer tube connectoris in operation located elevationally above the to-patient tubeconnector.
 7. The hemodialysis system of claim 1, wherein theto-dialyzer tube connector is in operation located elevationally abovethe from-patient tube connector.
 8. The hemodialysis system of claim 1,wherein the to-dialyzer tube connector is in operation locatedelevationally at the top of the blood cassette.
 9. The hemodialysissystem of claim 1, wherein at least one of the from-patient tubeconnector, to-patient tube connector, to-dialyzer tube connector, andfrom-dialyzer tube connector extends outwardly from an outer wall of thehousing to accept the respective tube.
 10. The hemodialysis system ofclaim 1, wherein the blood cassette further includes a blood pumpingtube for operable connection to the blood pump.
 11. The hemodialysissystem of claim 10, wherein the blood pumping tube is a linearperistaltic blood pumping tube.
 12. The hemodialysis system of claim 1,which includes at least one pressure sensor, and wherein the bloodcassette further includes at least one pressure sensing area positionedand arranged for operable engagement with the at least one pressuresensor.
 13. The hemodialysis system of claim 12, which includes arterialand venous pressure sensors and mating arterial and venous pressuresensing areas on the blood cassette.
 14. The hemodialysis system ofclaim 1, wherein lines internal to the housing of the blood cassette arevalved.
 15. The hemodialysis system of claim 1, wherein the bloodcassette and the dialysate cassette are integrated into a singlecassette.
 16. A hemodialysis system comprising: a dialyzer; a bloodpump; fresh and used dialysate pumps; a blood cassette including a rigidhousing and a flexible membrane attached to the rigid housing, the rigidhousing including a blood pumping tube operatively connected to theblood pump for pumping blood through the blood cassette, the housingfurther including a from-patient tube connector, a to-patient tubeconnector, a to-dialyzer tube connector, a from-dialyzer tube connector,a valve seat defined by the flexible membrane for opening and closing ato-patient line of the blood cassette, the to-patient line in fluidcommunication with the to-patient tube connector, a fresh dialysatepumping tube operatively connectable to the fresh dialysate pump, and aused dialysate pumping tube operatively connectable to the useddialysate pump; wherein the fresh and used dialysate pumps are operablewith a dialysate cassette separate from the blood cassette, thedialysate cassette in fluid communication with the dialyzer; and whereinat least one of the tube connectors is a tube port.
 17. The hemodialysissystem of claim 16, wherein the blood pumping tube, the fresh dialysatepumping tube and the used dialysate pumping tube are each linearperistaltic pumping tubes.
 18. A hemodialysis system comprising: adialyzer; a blood pump; fresh and used dialysate pumps; a cassetteincluding a rigid housing and a flexible membrane attached to the rigidhousing, the rigid housing including a blood pumping tube operativelyconnected to the blood pump for pumping blood through the cassette, thehousing further including a from-patient tube connector, a to-patienttube connector, a to-dialyzer tube connector, a from-dialyzer tubeconnector, a valve seat defined by the flexible membrane for opening andclosing a to-patient line of the cassette, the to-patient line in fluidcommunication with the to-patient tube connector, a fresh dialysatepumping tube operatively connectable to the fresh dialysate pump, and aused dialysate pumping tube operatively connectable to the useddialysate pump; and wherein the cassette further includes a vent to ventair removed from blood within the cassette.
 19. A hemodialysis systemcomprising: a dialyzer; a blood pump; fresh and used dialysate pumps; acassette including a rigid housing and a flexible membrane attached tothe rigid housing, the rigid housing including a blood pumping tubeoperatively connected to the blood pump for pumping blood through thecassette, the housing further including a from-patient tube connector, ato-patient tube connector, a to-dialyzer tube connector, a from-dialyzertube connector, a valve seat defined by the flexible membrane foropening and closing a to-patient line of the cassette, the to-patientline in fluid communication with the to-patient tube connector, a freshdialysate pumping tube operatively connectable to the fresh dialysatepump, and a used dialysate pumping tube operatively connectable to theused dialysate pump; and wherein the cassette includes an air separationchamber formed within the housing.
 20. A hemodialysis system comprising:a dialyzer; a blood pump; and a blood cassette including a housing and apumping tube, the pumping tube located outside of the housing andextending along a first side of the housing, the pumping tubeoperatively connected to the blood pump such that the blood pump inoperation contacts the pumping tube for pumping blood through thecassette, the housing including a from-patient tube connector, ato-patient tube connector, a saline/priming tube connector, ato-dialyzer tube connector, a from-dialyzer tube connector, and whereineach of the connectors extends along a side of the housing differentfrom the first side of the housing.
 21. The hemodialysis system of claim20, wherein each of the tube connectors extends along a side of thehousing opposing the first side of the housing.
 22. The hemodialysissystem of claim 20, wherein at least one of the tube connectors is atube port.
 23. The hemodialysis system of claim 20, wherein each of theconnectors is integral with and extends from the housing.